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WO2024183643A1 - 含抗tim-3抗体的药物组合 - Google Patents

含抗tim-3抗体的药物组合 Download PDF

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Publication number
WO2024183643A1
WO2024183643A1 PCT/CN2024/079622 CN2024079622W WO2024183643A1 WO 2024183643 A1 WO2024183643 A1 WO 2024183643A1 CN 2024079622 W CN2024079622 W CN 2024079622W WO 2024183643 A1 WO2024183643 A1 WO 2024183643A1
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WIPO (PCT)
Prior art keywords
antigen
antibody
binding fragment
amino acid
acid sequence
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PCT/CN2024/079622
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English (en)
French (fr)
Inventor
王训强
张喜全
于鼎
李许
汤湧
王欢
Original Assignee
正大天晴药业集团南京顺欣制药有限公司
正大天晴药业集团股份有限公司
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Application filed by 正大天晴药业集团南京顺欣制药有限公司, 正大天晴药业集团股份有限公司 filed Critical 正大天晴药业集团南京顺欣制药有限公司
Publication of WO2024183643A1 publication Critical patent/WO2024183643A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present disclosure belongs to the field of biomedicine, and specifically relates to a drug combination of an antibody that binds to TIM-3 and an antibody that binds to PD-1.
  • T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), also known as Hepatitis A Virus Cellular Receptor 2 (HAVCR2), is a member of the TIM family of immunoregulatory proteins (the human TIM family includes TIM-1, 3, and 4).
  • TIM-3 is selectively expressed on the surface of activated Th1 cells, and is also expressed on myeloid cells, DC cells, NK cells, macrophages, and also on a variety of tumor cells.
  • TIM-3 has a variety of different ligands, including galectin 9, phosphatidylserine (PtdSer), high mobility group protein B1 (HMGB1), and carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1).
  • TIM-3 As an immune checkpoint, TIM-3 has the physiological function of negatively regulating the body's immune response to avoid damage to the body by excessive immune or autoimmune responses. Increasing evidence indicates that TIM-3 protein and/or mRNA is upregulated in a variety of tumor tissues and tumor-associated immune cells, participating in tumor immune escape and immune response, and promoting tumor development.
  • PD-1 Programmed death-1 is a key immune checkpoint receptor expressed by activated T lymphocytes and B lymphocytes and mediates immunosuppression, and its ligands include PD-L1 and PD-L2.
  • Chinese patent document CN106977602A discloses an anti-PD-1 monoclonal antibody 14C12H1L1, which can effectively block the binding of PD-1 and PD-L1 and show good anti-tumor activity.
  • Head and neck cancer is a group of malignant tumors that occur widely in epithelial cells in the paranasal sinuses, nasal cavity, oral cavity and throat, of which more than 90% are head and neck squamous cell carcinoma (HNSCC).
  • HNSCC head and neck squamous cell carcinoma
  • the mortality rate of head and neck cancer in my country is much higher than that in other countries.
  • About 70%-80% of patients are in the locally advanced stage (i.e., stage III or IV) at the time of initial diagnosis. After radical treatment of the locally advanced stage, about 55% of patients will relapse or metastasize. Therefore, there is an urgent need to explore other drugs that can treat patients with head and neck cancer and improve the treatment effect.
  • Esophageal cancer is one of the common malignant tumors of the digestive system, and more than 90% of esophageal cancers are squamous cell carcinomas. Although standard treatment regimens can improve the clinical benefits of patients, most patients still have acquired drug resistance. Therefore, there is an urgent need to explore other drugs that can treat esophageal cancer patients and improve the treatment effect.
  • the present disclosure provides a drug combination, which includes an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, it also includes a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the drug combination includes a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination includes a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug.
  • the drug combination includes a unit dose of 60-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, a unit dose of 10-500 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, a unit dose of 2.5-100 mg of cisplatin and a unit dose of 30-150 mg of paclitaxel.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of 60-1800 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of 10-500 mg, carboplatin at a unit dose of 50-450 mg, and paclitaxel at a unit dose of 30-150 mg.
  • the drug combination comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and 10-800 mg of In some embodiments, the drug combination includes 100-1800 mg of anti-TIM-3 antibody or antigen binding fragment thereof, 10-800 mg of anti-PD-1 antibody or antigen binding fragment thereof and chemotherapy drugs. In some embodiments, the drug combination includes 100-1800 mg of anti-TIM-3 antibody or antigen binding fragment thereof, 10-800 mg of anti-PD-1 antibody or antigen binding fragment thereof, 30-100 mg/m 2 of cisplatin, and 75-175 mg/m 2 of paclitaxel.
  • the drug combination includes 100-1800 mg of anti-TIM-3 antibody or antigen binding fragment thereof, 10-800 mg of anti-PD-1 antibody or antigen binding fragment thereof, 2.5-5 mg/(mL/min) AUC of carboplatin, and 75-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, including 100-1800 mg of anti-TIM-3 antibody or its antigen-binding fragment and 10-800 mg of anti-PD-1 antibody or its antigen-binding fragment. In some embodiments, the drug combination is suitable for administration in a single treatment cycle, including 100-1800 mg of anti-TIM-3 antibody or its antigen-binding fragment, 10-800 mg of anti-PD-1 antibody or its antigen-binding fragment and chemotherapy drugs.
  • the drug combination is suitable for administration in a single treatment cycle, including 100-1800 mg of anti-TIM-3 antibody or its antigen-binding fragment, 10-800 mg of anti-PD-1 antibody or its antigen-binding fragment, 30-100 mg/m 2 of cisplatin, and 75-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, and comprises 100-1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg/(mL/min) AUC of carboplatin, and 75-175 mg/m 2 of paclitaxel.
  • the drug combination is used to treat a tumor.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering a therapeutically effective amount of a drug combination of the present disclosure to the subject.
  • the present disclosure also provides a method for first-line treatment of a tumor in a subject, comprising administering a therapeutically effective amount of a drug combination of the present disclosure to the subject.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering a therapeutically effective amount of a drug combination of the present disclosure to the subject in a first treatment phase, and administering a therapeutically effective amount of a drug combination of the present disclosure to the subject in a second treatment phase.
  • the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering a therapeutically effective amount of a drug combination of the present disclosure to the subject in a first treatment phase, and administering a therapeutically effective amount of a drug combination of the present disclosure to the subject in a second treatment phase.
  • the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a drug for treating a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure for treating a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure for first-line treatment of a tumor in a subject.
  • the use comprises administering a therapeutically effective amount of the drug combination of the present disclosure to the subject.
  • the use comprises administering a therapeutically effective amount of the drug combination of the present disclosure to the subject in a first treatment phase, and administering a therapeutically effective amount of the drug combination of the present disclosure to the subject in a second treatment phase.
  • the present disclosure also provides a method for treating tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the present disclosure also provides a method for treating tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug.
  • the present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the present disclosure also provides a method for first-line treatment of tumors, comprising administering to a subject a therapeutically effective amount of an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug.
  • the present disclosure provides a method for first-line treatment of tumors in a subject, comprising administering to the subject a therapeutically effective amount of the anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, and a chemotherapeutic drug in a first treatment phase, and administering to the subject a therapeutically effective amount of the anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, and a chemotherapeutic drug in a second treatment phase.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the preparation of a drug for treating tumors.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, and chemotherapeutic drugs in the preparation of drugs for treating tumors.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the preparation of drugs for first-line treatment of tumors.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, and chemotherapeutic drugs in the preparation of drugs for first-line treatment of tumors.
  • the chemotherapy drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapy drug is cisplatin and paclitaxel.
  • the chemotherapy drug is carboplatin and paclitaxel.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure in the preparation of a medicament for treating a tumor in a subject, wherein the medicament is used in combination with the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the present disclosure
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment disclosed in the present invention in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment disclosed in the present invention and a chemotherapeutic drug.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment disclosed in the present invention in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment disclosed in the present invention.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment disclosed in the present invention in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment disclosed in the present invention and a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In some embodiments, the chemotherapeutic drug is carboplatin and paclitaxel.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a combined drug combination of the present disclosure.
  • the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a combined drug combination of the present disclosure.
  • the present disclosure also provides the use of the combined drug combination of the present disclosure in the preparation of a drug for treating a tumor in a subject.
  • the present disclosure also provides the use of the combined drug combination of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject.
  • the present disclosure also provides the use of the combined drug combination of the present disclosure in the treatment of a tumor in a subject.
  • the present disclosure also provides the use of the combined drug combination of the present disclosure in the first-line treatment of a tumor in a subject.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof and the chemotherapeutic drug can be administered simultaneously, sequentially and/or alternately.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time.
  • the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the cisplatin is administered at a dose of 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 each time.
  • the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the carboplatin is administered at a dose of 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC each time.
  • the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, the paclitaxel is administered at a dose of 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 each time.
  • the present disclosure provides a kit for treating a tumor, which includes the drug combination of the present disclosure.
  • the kit includes an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, a chemotherapeutic drug is also included.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-TIM-3 antibody or an antigen-binding fragment thereof of the present disclosure.
  • the present disclosure also provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of The anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof in the preparation of a medicament for treating a tumor in a subject.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or antigen-binding fragment thereof in treating a tumor.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or an antigen-binding fragment thereof of the present disclosure and a chemotherapeutic drug.
  • the present disclosure also provides a method for first-line treatment of a tumor in a subject, comprising administering to the subject a therapeutically effective amount of an anti-PD-1 antibody or an antigen-binding fragment thereof of the present disclosure and a chemotherapeutic drug.
  • the present disclosure also provides the use of an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug in the preparation of a drug for treating a tumor in a subject.
  • the present disclosure also provides the use of an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug in the treatment of a tumor.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the tumor is a solid tumor. In some embodiments, the tumor is head and neck cancer. In some embodiments, the tumor is esophageal cancer.
  • the present disclosure provides a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, further comprising a chemotherapeutic drug.
  • the chemotherapy drugs include but are not limited to one or more of platinum anti-tumor drugs, taxane anti-tumor drugs, antimetabolite anti-tumor drugs, camptothecin anti-tumor drugs, nitrogen mustard anti-tumor drugs, anthracycline anti-tumor drugs, vinca alkaloid anti-tumor drugs, podophyllotoxin alkaloid anti-tumor drugs, and hormone anti-tumor drugs.
  • the chemotherapy drugs are platinum anti-tumor drugs and/or taxane anti-tumor drugs.
  • the chemotherapy drugs are platinum anti-tumor drugs and taxane anti-tumor drugs.
  • the chemotherapy drugs are cisplatin and paclitaxel. In other specific embodiments, the chemotherapy drugs are carboplatin and paclitaxel.
  • the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug. In some embodiments, the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug, and a taxane anti-tumor drug.
  • the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel. In other embodiments, the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin, and paclitaxel.
  • a combined drug combination which comprises:
  • a pharmaceutical combination of the present disclosure prepared to be suitable for administration to a subject during a second treatment phase.
  • the combination drug comprises:
  • a pharmaceutical combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug, which is prepared to be suitable for administration to a subject in a first treatment phase;
  • the combination drug comprises:
  • the combination drug comprises:
  • the combination drug comprises:
  • the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example: 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example: 4 treatment cycles, 5 treatment cycles, and/or 6 treatment cycles.
  • the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.
  • one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.
  • the second treatment phase is after the first treatment phase. In some embodiments, the second treatment phase is continued from the end of the first treatment phase until the patient loses clinical benefit, the toxicity is unacceptable, the efficacy is evaluated as disease progression (PD), and/or the investigator considers it inappropriate to continue the medication.
  • PD disease progression
  • the drug combination is packaged in the same kit, and the kit further includes instructions for using the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in combination to treat tumors.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the drug combination are separately packaged in their own medicine boxes, and the medicine box further includes instructions for using the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in combination to treat tumors.
  • the drug combination is packaged in the same kit, and the kit further includes instructions for combining anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, and chemotherapeutic drugs (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) to treat tumors.
  • chemotherapeutic drugs e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel
  • the anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, and chemotherapeutic drugs (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in the drug combination are packaged separately in their own medicine boxes, and the medicine box further includes instructions for combining anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, and chemotherapeutic drugs (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) to treat tumors.
  • chemotherapeutic drugs e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel
  • the drug combination is a fixed combination.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the fixed combination are formulated in a single preparation.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is in the form of a liquid preparation or a solid preparation.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is an injection.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the drug combination is a non-fixed combination.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment in the non-fixed combination are each in the form of a pharmaceutical composition.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and the chemotherapeutic drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) in the non-fixed combination are each in the form of a pharmaceutical composition.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment in the non-fixed combination, is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is an injection. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment in the non-fixed combination, is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is an injection. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single preparation.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment is a liquid preparation or a solid preparation.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment is an injection.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the pharmaceutical composition containing the chemotherapeutic drug is a liquid preparation or a solid preparation.
  • the pharmaceutical composition containing cisplatin is a liquid preparation.
  • the pharmaceutical composition containing cisplatin is an injection.
  • the pharmaceutical composition containing cisplatin is a solid preparation.
  • the pharmaceutical composition containing cisplatin is a lyophilized preparation.
  • the pharmaceutical composition containing cisplatin is a powder injection preparation.
  • the pharmaceutical composition containing carboplatin is a liquid preparation.
  • the pharmaceutical composition containing carboplatin is an injection.
  • the pharmaceutical composition containing carboplatin is a solid preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder injection preparation. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is an injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a powder injection preparation.
  • the present disclosure also aims to provide a drug package, which contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container includes a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, it further comprises one or more other containers, and the other containers include a pharmaceutical composition containing a chemotherapeutic drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel).
  • a chemotherapeutic drug e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel
  • the present disclosure also aims to provide a drug package, which contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, it further comprises one or more other containers, and the other containers include a pharmaceutical composition containing a chemotherapeutic drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel).
  • a chemotherapeutic drug e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel
  • the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg. In some embodiments, the unit dose of the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 840 mg, about 880 mg, about 900 mg, about 920 mg, about 9 1500 mg, about 1520 mg, about 1560 mg, about 1600 mg, about 1620 mg, about 1640 mg, about 1680 mg, about 1720
  • the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is about 240 mg, about 300 mg, about 360 mg and/or about 600 mg. In some embodiments, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is about 240 mg and/or about 600 mg.
  • the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg. In some embodiments, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, About 250mg, about 260mg, about 270mg, about 280mg, about 290mg, about 300mg, about 310mg, about 320mg, about 330mg, about 340mg, about 350mg, about 360mg, about 370mg, about 380
  • the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the drug combination is about 100mg and/or about 200mg. In some embodiments, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment in the drug combination is about 100mg.
  • the drug combination further comprises a chemotherapeutic drug.
  • the chemotherapeutic drugs are cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drugs are carboplatin and paclitaxel.
  • the unit dose of cisplatin in the drug combination is 1-200 mg or 2.5-100 mg. In some embodiments, the unit dose of cisplatin in the drug combination is 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and/or 100 mg. In some embodiments, the unit dose of cisplatin in the drug combination is 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg.
  • the unit dose of carboplatin in the drug combination is 10- In some embodiments, the unit dose of carboplatin in the pharmaceutical combination is 50 mg, 100 mg, 150 mg, 250 mg and/or 450 mg. In some embodiments, the unit dose of paclitaxel in the pharmaceutical combination is 10-300 mg or 30-150 mg. In some embodiments, the unit dose of paclitaxel in the pharmaceutical combination is 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg, and an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg.
  • the pharmaceutical combination comprises a unit dose of about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 840 mg, about 880 mg, about 900 mg.
  • the invention relates to an anti-TIM-3 antibody or antigen-binding fragment thereof of about 1740 mg, about 1760 mg and/or about 1800 mg, or a range formed by any of the foregoing values, and a unit dose of about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about
  • the drug combination includes an anti-TIM-3 antibody or its antigen-binding fragment in a unit dose of about 240 mg, about 300 mg, about 360 mg, and/or about 600 mg, and an anti-PD-1 antibody or its antigen-binding fragment in a unit dose of about 100 mg and/or about 200 mg.
  • the drug combination includes an anti-TIM-3 antibody or its antigen-binding fragment in a unit dose of about 240 mg and/or about 600 mg, and an anti-PD-1 antibody or its antigen-binding fragment in a unit dose of about 100 mg.
  • the drug combination further comprises cisplatin in a unit dose of 1-200 mg or 2.5-100 mg, and paclitaxel in a unit dose of 10-300 mg or 30-150 mg. In some embodiments, the drug combination further comprises cisplatin in a unit dose of 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and/or 100 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg. In some embodiments, the drug combination further comprises cisplatin in a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination further comprises carboplatin in a unit dose of 10-500 mg or 50-450 mg, and paclitaxel in a unit dose of 10-300 mg or 30-150 mg. In other embodiments, the drug combination further comprises carboplatin in a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and/or 450 mg, and paclitaxel in a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg, about 300 mg, about 360 mg and/or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg and/or about 200 mg, cisplatin at a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg and/or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg, cisplatin at a unit dose of 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg, about 300 mg, about 360 mg and/or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg and/or about 200 mg, a carboplatin at a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and/or 450 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination comprises an anti-TIM-3 antibody or an antigen-binding fragment thereof at a unit dose of about 240 mg and/or about 600 mg, an anti-PD-1 antibody or an antigen-binding fragment thereof at a unit dose of about 100 mg, carboplatin at a unit dose of 50 mg, 100 mg, 150 mg, 250 mg and/or 450 mg, and paclitaxel at a unit dose of 30 mg, 60 mg, 100 mg and/or 150 mg.
  • the drug combination includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of anti-TIM-3 antibodies or antigen-binding fragments thereof. In some embodiments, the drug combination includes about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or an anti-TIM-3 antibody or antigen-binding fragment thereof in a range formed by any of the above values. In some embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibodies or antigen-binding fragments thereof. In some embodiments, the pharmaceutical combination includes about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the drug combination includes 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination includes about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg, or an anti-PD-1 antibody or an antigen-binding fragment thereof in a range formed by any of the above values. In some embodiments, the drug combination includes about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination further comprises a chemotherapeutic drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the drug combination further comprises 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 of cisplatin, or 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin.
  • the drug combination further comprises about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2 , about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , or about 100 mg/m 2.
  • cisplatin in the range formed by any of the above values, or carboplatin in the range of about 2.5mg/(mL/min)AUC, about 3mg/(mL/min)AUC, about 3.2mg/(mL/min)AUC, about 3.5mg/(mL/min)AUC, about 3.75mg/(mL/min)AUC, about 4mg/(mL/min)AUC, about 4.5mg/(mL/min)AUC, or about 5mg/(mL/min)AUC, or any of the above values.
  • the drug combination further includes 48-75mg/m 2 of cisplatin, or 3.2-5mg/(mL/min)AUC of carboplatin. In some embodiments, the drug combination further comprises about 48 mg/m 2 , about 60 mg/m 2 , or about 75 mg/m 2 of cisplatin, or about 3.2 mg/(mL/min) AUC, about 4 mg/(mL/min) AUC, or about 5 mg/(mL/min) AUC of carboplatin. In some embodiments, the drug combination further comprises about 75 mg/m 2 of cisplatin, or about 5 mg/(mL/min) AUC of carboplatin.
  • the drug combination further comprises 30-75 mg/m 2 of cisplatin. In some embodiments, the drug combination further comprises 60-75 mg/m 2 of cisplatin. In some embodiments, the drug combination further comprises about 60 mg/m 2 of cisplatin. In some embodiments, the drug combination further comprises about 75 mg/m 2 of cisplatin. In some embodiments, the drug combination further comprises 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 of paclitaxel.
  • the drug combination further comprises about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2 , about 109 mg/m 2 , about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 145 mg/m 2 , about 150 mg/m 2 or about 175 mg/m 2 , or a range formed by any of the above values of paclitaxel. In some embodiments, the drug combination further comprises 112-175 mg/m 2 of paclitaxel.
  • the drug combination further comprises about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 150 mg/m 2 , or about 175 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises about 175 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises 67.5-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises 135-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises about 135 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises about 150 mg/m 2 of paclitaxel.
  • the drug combination comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg, or about 1800 mg, or a range formed by any of the above values of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and about 1
  • the composition comprises about 1200 mg or about 1500 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.
  • the composition comprises about 1200 mg or about 1500 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.
  • the drug combination comprises about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, and about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof.
  • the drug combination further comprises 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 of cisplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 of paclitaxel.
  • the drug combination further comprises about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2 , about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , or about 100 mg/m 2 , or a range formed by any of the foregoing values of cisplatin, and about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2
  • the drug combination further comprises 48-75 mg/m 2 of cisplatin, and 112-175 mg/m 2 of paclitaxel.
  • the drug combination further comprises about 75 mg/m 2 of cisplatin, and about 175 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises 30-75 mg/m 2 of cisplatin , and 67.5-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises 60-75 mg/m 2 of cisplatin, and 135-175 mg / m 2 of paclitaxel. In some embodiments, the drug combination further comprises 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination further comprises about 60 mg/m 2 or about 75 mg/m 2 of cisplatin, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel.
  • the drug combination further comprises 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 of paclitaxel.
  • the drug combination further comprises about 2.5 mg/(mL/min) AUC, about 3 mg/(mL/min) AUC, about 3.2 mg/(mL/min) AUC, about 3.5 mg/(mL/min) AUC, about 3.75 mg/(mL/min) AUC, about 4 mg/(mL/min) AUC, about 4.5 mg/(mL/min) AUC, or about 5 mg/(mL/min) AUC, or a range formed by any of the foregoing values, and about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2 , about 109 mg/m 2 , about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 145 mg/m 2 , about 150 mg/m 2 , or about 175 mg/m 2 , or paclitaxel in the range formed by any of the above values.
  • the drug combination further comprises 3.2-5 mg/(mL/min) AUC of carboplatin, and 112-175 mg/m 2 of paclitaxel. In other embodiments, the drug combination further comprises about 5 mg/(mL/min) AUC of carboplatin, and about 175 mg/m 2 of paclitaxel.
  • the drug combination further comprises cisplatin and paclitaxel.
  • the drug combination comprises 100-1800mg, 600-1800mg, 600-1500mg, or 1200-1500mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800mg, 50-500mg, or 100-200mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100mg/m 2 , 30-75mg/m 2 , 48-75mg/m 2 or 60-75mg/m 2 of cisplatin, and 75-175mg/m 2 , 100-175mg/m 2 , 112-175mg/m 2 or 135-175mg/m 2 of paclitaxel.
  • the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 48-75 mg/m 2 of cisplatin, and 112-175 mg/m 2 of paclitaxel. In some specific embodiments, the drug combination includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, about 75 mg/m 2 of cisplatin, and about 175 mg/m 2 of paclitaxel.
  • the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 30-75 mg/m 2 of cisplatin, and 67.5-150 mg/m 2 of paclitaxel. In some specific embodiments, the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-175 mg/m 2 of paclitaxel.
  • the drug combination includes about 1200 mg or about 1500 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel. In some specific embodiments, the drug combination includes about 1200 mg of anti-TIM-3 antibody or antigen-binding fragment thereof, about 200 mg of anti-PD-1 antibody or antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel.
  • the drug combination includes about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, about 60 mg/m 2 or about 75 mg/m 2 of cisplatin, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel.
  • the drug combination further comprises carboplatin and paclitaxel.
  • the drug combination comprises 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg/(mL/min) AUC or 3.2- 5mg/(mL/min)AUC carboplatin, and 75-175mg/m 2 , 100-175mg/m 2 , 112-175mg/m 2 or 135-175mg/m 2 of paclitaxel.
  • the drug combination includes about 1200mg or about 1500mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 3.2-5mg/(mL/min)AUC carboplatin, and 112-175mg/m 2 of paclitaxel. In other specific embodiments, the drug combination includes about 1200mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, about 5mg/(mL/min)AUC carboplatin, and about 175mg/m 2 of paclitaxel.
  • the content of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is a daily dose. In some embodiments, the content of the anti-TIM-3 antibody or its antigen-binding fragment in the pharmaceutical combination is a once-a-day dose.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof in the pharmaceutical combination is present in a uniform dose.
  • the content of the anti-TIM-3 antibody or its antigen-binding fragment in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.
  • the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is a daily dose. In some embodiments, the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical combination is a once-a-day dose.
  • the anti-PD-1 antibody or antigen-binding fragment thereof in the pharmaceutical combination is contained in a uniform dose.
  • the content of the anti-PD-1 antibody or its antigen-binding fragment in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.
  • the amount of cisplatin in the pharmaceutical combination is a daily dose. In some embodiments, the amount of cisplatin in the pharmaceutical combination is a once-a-day dose.
  • the content of cisplatin in the drug combination is a dosage for one treatment cycle, and each treatment cycle is 3 weeks.
  • the content of carboplatin in the pharmaceutical combination is a daily dose. In some embodiments, the content of carboplatin in the pharmaceutical combination is a once-daily dose.
  • the content of carboplatin in the drug combination is a dosage for one treatment cycle, and each treatment cycle is 3 weeks.
  • the content of paclitaxel in the pharmaceutical combination is a daily dose. In some embodiments, the content of paclitaxel in the pharmaceutical combination is a once-a-day dose.
  • the content of paclitaxel in the drug combination is a dose for one treatment cycle, and each treatment cycle is 3 weeks.
  • the drug combination is suitable for administration in a single treatment cycle, and includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or its antigen-binding fragment. In some embodiments, the drug combination is suitable for administration in a single treatment cycle, and includes about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or an anti-TIM-3 antibody or its antigen-binding fragment in a range formed by any of the above values.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof. In some embodiments, the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof.
  • the drug combination is suitable for administration in a single treatment cycle, and includes 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination is suitable for administration in a single treatment cycle, and includes about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg, or an anti-PD-1 antibody or an antigen-binding fragment thereof in a range formed by any of the above values.
  • the pharmaceutical combination is suitable for administration in a single treatment cycle and includes about 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises a chemotherapeutic agent.
  • the chemotherapeutic agent is cisplatin and paclitaxel.
  • the chemotherapeutic agent is carboplatin and paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 of cisplatin, or 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2, about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , or about 100 mg/m 2 , or any of the foregoing.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 48-75 mg/m 2 of cisplatin, or 3.2-5 mg/(mL/min) AUC of carboplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 48 mg/m 2 , about 60 mg/m 2 , or about 75 mg/m 2 of cisplatin, or about 3.2 mg/(mL/min) AUC, about 4 mg/(mL/min) AUC, or about 5 mg/(mL/min) AUC of carboplatin.
  • the drug combination is suitable for administration in a single treatment cycle and further includes about 75 mg/m 2 of cisplatin, or about 5 mg/(mL/min) AUC of carboplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 30-75 mg/m 2 of cisplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 60-75 mg/m 2 of cisplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes about 60 mg/m 2 of cisplatin. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 75 mg/m 2 of cisplatin.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2, about 109 mg/m 2 , about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 145 mg/m 2 , about 150 mg/m 2 , or about 175 mg/m 2 , or a range formed by any of the above values of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further includes 112-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further includes about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , 150 mg/m 2 , or about 175 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes about 175 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 67.5-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further includes 135-150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further includes about 135 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises about 150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, and includes an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination is suitable for administration in a single treatment cycle, and includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical combination is suitable for administration in a single treatment cycle and comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the above values of an anti-TIM-3 antibody or its antigen binding protein.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment.
  • the drug combination is suitable for administration in a single treatment cycle, and includes about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 30-100 mg/ m2 , 30-75 mg/ m2 , 48-75 mg/ m2 , or 60-75 mg/ m2 of cisplatin and 75-175 mg/ m2 , 100-175 mg/ m2 , 112-175 mg/ m2 , or 135-175 mg/ m2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2 , about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , or about 100 mg/m 2 , or a range formed by any of the foregoing values of cisplatin, and about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 48-75 mg/m 2 of cisplatin and 112-1
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 75 mg/m 2 of cisplatin and 175 mg/ m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 75 mg/m 2 of cisplatin and 175 mg/m 2 of paclitaxel . The combination is suitable for administration in a single treatment cycle and also includes 30-75 mg/m 2 of cisplatin, and 67.5-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and also includes 60-75 mg/m 2 of cisplatin, and 135-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and also includes 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and also includes about 60 mg/m 2 or about 75 mg/m 2 of cisplatin, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin and 75-175 mg/ m2 , 100-175 mg/ m2 , 112-175 mg/ m2 or 135-175 mg/ m2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle and further comprises about 2.5 mg/(mL/min) AUC, about 3 mg/(mL/min) AUC, about 3.2 mg/(mL/min) AUC, about 3.5 mg/(mL/min) AUC, about 3.75 mg/(mL/min) AUC, about 4 mg/(mL/min) AUC, about 4.5 mg/(mL/min) AUC, or about 5 mg/(mL/min) AUC, or a range formed by any of the foregoing values of carboplatin, and about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2 , about 109 mg/m 2 , about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 145 mg/m 2 , about 150 mg/m 2 2 or about 175 mg/m 2 , or a range formed by any of the above values
  • the drug combination is suitable for administration in a single treatment cycle and further comprises 3.2-5 mg/(mL/min) AUC of carboplatin, and 112-175 mg/m 2 of paclitaxel. In some embodiments, the drug combination is suitable for administration in a single treatment cycle and further comprises 5 mg/(mL/min) AUC of carboplatin, and 175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, and includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin, and paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, and includes 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 of cisplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 48-75 mg/m 2 of cisplatin, and 112-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 75 mg/m 2 of cisplatin, and 175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-75 mg/m 2 of cisplatin, and 67.5-150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, about 60 mg/m 2 or about 75 mg/m 2 of cisplatin, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel.
  • the drug combination is suitable for use in a single treatment cycle, including anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, carboplatin and paclitaxel.
  • the drug combination is suitable for use in a single treatment cycle, including 100-1800mg, 600-1800mg, 600-1500mg, or 1200-1500mg of anti-TIM-3 antibodies or antigen-binding fragments thereof, 10-800mg, 50-500mg, or 100-200mg of anti-PD-1 antibodies or antigen-binding fragments thereof, 2.5-5mg/(mL/min)AUC or 3.2-5mg/(mL/min)AUC of carboplatin, and 75-175mg/ m2 , 100-175mg/ m2 , 112-175mg/ m2 or 135-175mg/ m2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 3.2-5 mg/(mL/min) AUC of carboplatin, and 112-175 mg/m 2 of paclitaxel.
  • the drug combination is suitable for administration in a single treatment cycle, comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 5 mg/(mL/min) AUC of carboplatin, and 175 mg/m 2 of paclitaxel.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 of cisplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 of paclitaxel, which is prepared to be administered to a subject in a single treatment cycle in a first treatment period; and
  • a drug combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be administered to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 48-75 mg/m 2 of cisplatin, and 112-175 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 75 mg/m 2 of cisplatin, and 175 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-75 mg/m 2 of cisplatin, and 67.5-150 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-175 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to a subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to a subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 60-75 mg/m 2 of cisplatin, and 135-150 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, about 60 mg/m 2 or about 75 mg/m 2 of cisplatin, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel, which is prepared to be administered to a subject in a single treatment cycle in a first treatment phase;
  • a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 of paclitaxel, which is prepared to be administered to a subject in a single treatment cycle in a first treatment period; and
  • a drug combination comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, and 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be administered to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • the invention relates to a drug combination of about 100 mg, about 1700 mg or about 1800 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, or a range formed by any of the foregoing values, and about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg or about 800 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, or a range formed by any of the foregoing values,
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 3.2-5 mg/(mL/min) AUC of carboplatin, and 112-175 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg or about 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the present disclosure provides a combination drug combination comprising:
  • a drug combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 5 mg/(mL/min) AUC of carboplatin, and 175 mg/m 2 of paclitaxel, which is prepared to be suitable for administration to a subject in a single treatment cycle in a first treatment phase; and
  • a pharmaceutical combination comprising about 1200 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof and about 200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, which is prepared to be suitable for administration to the subject in a single treatment cycle in the second treatment phase.
  • the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example: 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example: 4 treatment cycles, 5 treatment cycles, and/or 6 treatment cycles.
  • the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.
  • one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.
  • the second treatment phase is after the first treatment phase. In some embodiments, the second treatment phase is continued from the end of the first treatment phase until the patient loses clinical benefit, the toxicity is unacceptable, the efficacy is evaluated as PD, and/or the investigator considers it inappropriate to continue the medication.
  • the anti-TIM-3 antibody or its antigen-binding fragment may be a pharmaceutical composition containing an anti-TIM-3 antibody or its antigen-binding fragment.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is a single dose or multiple doses, preferably multiple doses.
  • the multiple doses may be composed of a single dose of a pharmaceutical composition containing about 240 mg, about 300 mg, about 360 mg and/or about 600 mg of an anti-TIM-3 antibody or its antigen-binding fragment.
  • the multiple doses may be composed of a single dose of a pharmaceutical composition containing about 240 mg and/or about 600 mg of an anti-TIM-3 antibody or its antigen-binding fragment.
  • the anti-PD-1 antibody or antigen-binding fragment thereof may be a pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof.
  • the pharmaceutical composition containing the anti-PD-1 antibody or antigen-binding fragment thereof is a single dose or multiple doses, preferably multiple doses.
  • the multiple doses may consist of a single dose of a pharmaceutical composition containing about 100 mg and/or about 200 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.
  • the multiple doses may consist of a single dose of a pharmaceutical composition containing about 100 mg of an anti-PD-1 antibody or antigen-binding fragment thereof.
  • the chemotherapeutic drug can be a pharmaceutical composition containing the chemotherapeutic drug.
  • the pharmaceutical composition containing the chemotherapeutic drug is a single dose or multiple doses, preferably multiple doses.
  • the chemotherapeutic drug is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drug is carboplatin and paclitaxel.
  • the cisplatin may be a pharmaceutical composition containing cisplatin.
  • the pharmaceutical composition containing cisplatin is a single dose or multiple doses, preferably multiple doses.
  • the multiple doses may consist of a single dose of a pharmaceutical composition containing 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and/or 100 mg of cisplatin.
  • the multiple doses may consist of a single dose of a pharmaceutical composition containing 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg of cisplatin.
  • the carboplatin may be a pharmaceutical composition containing carboplatin.
  • the pharmaceutical composition containing carboplatin is a single dose or multiple doses, preferably multiple doses.
  • the multiple doses may be a single dose containing 50 mg, 100 mg, 150 mg, 250 mg, and/or 450 mg of carboplatin.
  • the paclitaxel may be a pharmaceutical composition containing paclitaxel.
  • the pharmaceutical composition containing paclitaxel is a single dose or multiple doses, preferably multiple doses.
  • the multiple doses may consist of a single dose of a pharmaceutical composition containing 30 mg, 60 mg, 100 mg and/or 150 mg of paclitaxel.
  • the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment: the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1; wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be packaged separately or together.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are packaged separately, wherein the anti-TIM-3 antibody or its antigen-binding fragment can be packaged in a single portion or multiple portions, and the anti-PD-1 antibody or its antigen-binding fragment can be packaged in a single portion or multiple portions.
  • the anti-TIM-3 antibody or its antigen-binding fragment can be packaged in a single portion or multiple portions (e.g., 2 portions, 3 portions, 4 portions, 5 portions, 6 portions, 7 portions, 8 portions or more portions), and the anti-PD-1 antibody or its antigen-binding fragment can be packaged in a single portion or multiple portions (e.g., 2 portions or other portions).
  • the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof to a patient, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof to a patient.
  • the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared to be suitable for administering to a patient about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range of any of the above values of anti-TI
  • a pharmaceutical composition containing an anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to a patient a single dose or multiple doses of an anti-PD-1 antibody or its antigen-binding fragment of
  • the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the pharmaceutical combination comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the pharmaceutical composition comprising the anti-TIM-3 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 1200 mg of the anti-TIM-3 antibody or an antigen-binding fragment thereof, and the pharmaceutical composition comprising the anti-PD-1 antibody or an antigen-binding fragment thereof is prepared as a single dose or multiple doses suitable for administering to a patient about 200 mg of the anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug combination further comprises a chemotherapeutic drug.
  • the chemotherapeutic drugs are cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drugs are carboplatin and paclitaxel.
  • the drug combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 of cisplatin to a patient
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition comprising cisplatin and a pharmaceutical composition comprising paclitaxel
  • the pharmaceutical composition comprising cisplatin is prepared to be suitable for administration to a patient at about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2 , about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg /m 2 , about 80 mg/m 2 , about 90 mg/m 2 or about 100 mg/m 2 , or a single dose or multiple doses of cisplatin in the range of any of the above values, and the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to the patient a single dose or multiple doses of c
  • the The pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 48-75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 112-175 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 175 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 30-75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 67.5-150 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 60-75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 135-175 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering 60-75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering 135-150 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition containing cisplatin and a pharmaceutical composition containing paclitaxel, wherein the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering about 60 mg/m 2 or about 75 mg/m 2 of cisplatin to a patient, and the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel to a patient.
  • the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel
  • the pharmaceutical composition comprising carboplatin is prepared as a single dose or multiple doses suitable for administering to a patient 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin
  • the pharmaceutical composition comprising paclitaxel is prepared as a single dose or multiple doses suitable for administering to a patient 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 of paclitaxel.
  • the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel
  • the pharmaceutical composition comprising carboplatin is prepared to be suitable for administering to a patient a single dose or multiple doses of carboplatin of about 2.5 mg/(mL/min) AUC, about 3 mg/(mL/min) AUC, about 3.2 mg/(mL/min) AUC, about 3.5 mg/(mL/min) AUC, about 3.75 mg/(mL/min) AUC, about 4 mg/(mL/min) AUC, about 4.5 mg/(mL/min) AUC, or about 5 mg/(mL/min) AUC, or a range formed by any of the above values
  • the pharmaceutical composition comprising paclitaxel is prepared to be suitable for administering to a patient about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2 , about 109 mg/m 2
  • the pharmaceutical combination further comprises a pharmaceutical composition comprising carboplatin and a pharmaceutical composition comprising paclitaxel, wherein the pharmaceutical composition comprising carboplatin is prepared as a single dose or multiple doses suitable for administering to a patient 5 mg/(mL/min) AUC of carboplatin, and the pharmaceutical composition comprising paclitaxel is prepared as a single dose or multiple doses suitable for administering to a patient 175 mg/m 2 of paclitaxel.
  • the drug combination includes a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition comprising cisplatin, and a pharmaceutical composition comprising paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared to be suitable for administering to the patient a single dose or multiple doses of 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to the patient 75-175 mg/m 2 ,
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared to be suitable for administering to the patient a single dose or multiple doses of 48-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to the patient a single dose or multiple doses of 112-175 mg/m 2 of paclitaxel.
  • the drug composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a suitable
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 75 mg/ m2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 175 mg/ m2 of paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 30-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 67.5-150 mg/m 2 of paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 60-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 135-175 mg/m 2 of paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 60-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 135-150 mg/m 2 of paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient 60-75 mg/m 2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 135-150 mg/m 2 of paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing cisplatin is prepared as a single dose or multiple doses suitable for administering to the patient about 60 mg/ m2 or about 75 mg/ m2 of cisplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient about 135 mg/ m2 or about 150 mg/ m2 of paclitaxel.
  • the drug combination includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing carboplatin, and a pharmaceutical composition containing paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of about 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing carboplatin is prepared to be suitable for administering to the patient a single dose or multiple doses of 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin
  • the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to the patient 75-175 mg/m 2 , 100-175 mg/m
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of about 1200mg or about 1500mg anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing anti-PD-1 antibody or its antigen-binding fragment is prepared to be suitable for administering to the patient a single dose or multiple doses of about 200mg anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing carboplatin is prepared to be suitable for administering to the patient a single dose or multiple doses of 3.2-5mg/(mL/min)AUC of carboplatin
  • the pharmaceutical composition containing paclitaxel is prepared to be suitable for administering to the patient a single dose or multiple doses of 112-175mg/m 2 paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 1200 mg of the anti-TIM-3 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is prepared as a single dose or multiple doses suitable for administering to the patient about 200 mg of the anti-PD-1 antibody or its antigen-binding fragment
  • the pharmaceutical composition containing carboplatin is prepared as a single dose or multiple doses suitable for administering to the patient 5 mg/(mL/min) AUC of carboplatin
  • the pharmaceutical composition containing paclitaxel is prepared as a single dose or multiple doses suitable for administering to the patient 175 mg/ m2 of paclitaxel.
  • the present disclosure provides a kit for treating a tumor, the kit comprising a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, and instructions for using the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and the pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof in combination to treat the tumor.
  • the kit includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, and a pharmaceutical composition containing a chemotherapeutic drug, as well as instructions for using the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, and a pharmaceutical composition containing a chemotherapeutic drug in combination to treat a tumor.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel. In other embodiments, the chemotherapeutic drug is carboplatin and paclitaxel.
  • the kit includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing cisplatin or carboplatin, and a pharmaceutical composition containing paclitaxel, as well as instructions for using the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, the pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, the pharmaceutical composition containing cisplatin or carboplatin, and the pharmaceutical composition containing paclitaxel in combination to treat a tumor.
  • the present disclosure provides a kit for treating a tumor, the kit comprising a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, and instructions for using the pharmaceutical composition to treat a tumor.
  • the kit includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof and a pharmaceutical composition containing a chemotherapeutic drug, and instructions for combining the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof with a pharmaceutical composition containing a chemotherapeutic drug to treat tumors.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the kit includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing cisplatin or carboplatin, and a pharmaceutical composition containing paclitaxel, and instructions for combining the pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, a pharmaceutical composition containing cisplatin or carboplatin, and a pharmaceutical composition containing paclitaxel to treat tumors.
  • the present disclosure also provides a drug package for treating tumors, which contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container includes a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, it also includes one or more other containers, and the other containers include a pharmaceutical composition containing a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the drug package contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, and the second container includes a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug package comprises single-packaged pharmaceutical compositions in separate containers, wherein the first container comprises a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof, the second container comprises a pharmaceutical composition containing an anti-PD-1 antibody or an antigen-binding fragment thereof, the third container comprises a pharmaceutical composition containing cisplatin or carboplatin, and the fourth container comprises a pharmaceutical composition containing paclitaxel.
  • the present disclosure also provides a drug package for treating tumors, which contains single-packaged pharmaceutical compositions in separate containers, wherein the first container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof; optionally, it also includes one or more other containers, and the other containers include a pharmaceutical composition containing a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the drug package contains a single-packaged pharmaceutical composition in a separate container, wherein the container includes a pharmaceutical composition containing an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof.
  • the drug package comprises single-packaged pharmaceutical compositions in separate containers, wherein the first container comprises a pharmaceutical composition comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, the second container comprises a pharmaceutical composition comprising cisplatin or carboplatin, and the third container comprises a pharmaceutical composition comprising paclitaxel.
  • the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment in the kit or drug package is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is an injection. In some specific embodiments, the pharmaceutical composition containing the anti-TIM-3 antibody or antigen-binding fragment thereof is a lyophilized preparation.
  • the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment in the kit or drug package is a liquid preparation or a solid preparation. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is an injection. In some specific embodiments, the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is a liquid preparation or a solid preparation.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is an injection.
  • the pharmaceutical composition containing anti-TIM-3 antibody or its antigen-binding fragment and anti-PD-1 antibody or its antigen-binding fragment is a lyophilized preparation.
  • the pharmaceutical composition containing the chemotherapeutic drug is a liquid preparation or a solid preparation.
  • the pharmaceutical composition containing cisplatin is a liquid preparation.
  • the pharmaceutical composition containing cisplatin is an injection.
  • the pharmaceutical composition containing cisplatin is a solid preparation.
  • the pharmaceutical composition containing cisplatin is a lyophilized preparation.
  • the pharmaceutical composition containing cisplatin is a powder injection preparation.
  • the pharmaceutical composition containing carboplatin is a liquid preparation.
  • the pharmaceutical composition containing carboplatin is an injection. In some specific embodiments, the pharmaceutical composition containing carboplatin is a solid preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder injection preparation. In some specific embodiments, in the kit or drug package, the pharmaceutical composition containing paclitaxel is a liquid preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is an injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a powder injection preparation.
  • the tumor is a solid tumor.
  • the solid tumor is head and neck cancer.
  • the solid tumor is esophageal cancer.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject.
  • the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject.
  • the present disclosure also provides a method for treating a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject in a first treatment phase, and administering a drug combination of the present disclosure to the subject in a second treatment phase.
  • the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject.
  • the present disclosure provides a method for first-line treatment of a tumor in a subject, comprising administering a drug combination of the present disclosure to the subject in a first treatment phase, and administering a drug combination of the present disclosure to the subject in a second treatment phase.
  • the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a drug for treating a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure for treating a tumor in a subject.
  • the present disclosure also provides the use of the drug combination of the present disclosure for first-line treatment of a tumor in a subject.
  • the use includes administering the drug combination of the present disclosure to a subject.
  • the use includes administering the drug combination of the present disclosure to a subject in a first treatment phase, and administering the drug combination of the present disclosure to a subject in a second treatment phase.
  • the present disclosure also provides a method for treating tumors, comprising administering the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure to a subject.
  • the present disclosure also provides a method for treating tumors, comprising administering the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic drug to a subject.
  • the present disclosure also provides a method for first-line treatment of tumors, comprising administering the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure to a subject.
  • the present disclosure also provides a method for first-line treatment of tumors, comprising administering the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic drug to a subject.
  • the present disclosure provides a method for first-line treatment of tumors in a subject, comprising administering the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic drug to a subject in a first treatment stage, and administering the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure to a subject in a second treatment stage.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating tumors.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and a chemotherapeutic drug in the preparation of a drug for treating tumors.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of tumors.
  • the present disclosure also provides the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure Use of fragments and chemotherapeutic drugs in the preparation of drugs for first-line treatment of tumors.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel.
  • the chemotherapeutic drug is carboplatin and paclitaxel.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for treating a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure.
  • the present disclosure also provides the use of the anti-PD-1 antibody or its antigen-binding fragment of the present disclosure in the preparation of a drug for first-line treatment of a tumor in a subject, wherein the drug is used in combination with the anti-TIM-3 antibody or its antigen-binding fragment of the present disclosure and a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug. In some embodiments, the chemotherapeutic drug is cisplatin and paclitaxel. In some embodiments, the chemotherapy drugs are carboplatin and paclitaxel.
  • the drug combination in the method or use, includes an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof. In some embodiments, in the method or use, the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug.
  • the chemotherapeutic drug includes but is not limited to platinum anti-tumor drugs, taxane anti-tumor drugs, anti-metabolism anti-tumor drugs, camptothecin anti-tumor drugs, nitrogen mustard anti-tumor drugs, anthracycline anti-tumor drugs, vinca alkaloid anti-tumor drugs, podophyllotoxin alkaloid anti-tumor drugs, and hormone anti-tumor drugs.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel. In other specific embodiments, the chemotherapeutic drug is carboplatin and paclitaxel.
  • the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug and a taxane anti-tumor drug.
  • the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin and paclitaxel.
  • the drug combination includes an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin and paclitaxel.
  • it comprises administering to the subject a therapeutically effective amount of the pharmaceutical combination of the present disclosure in a first treatment phase, and administering to the subject a therapeutically effective amount of the pharmaceutical combination of the present disclosure in a second treatment phase.
  • the method or use in the method or use, it includes administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination including an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug; and
  • a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof is administered to the subject.
  • it comprises administering to the subject in the first treatment stage a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, a platinum anti-tumor drug and a taxane anti-tumor drug; and
  • a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof is administered to the subject.
  • it comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, cisplatin and paclitaxel; and
  • a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof is administered to the subject.
  • it comprises administering to the subject in a first treatment phase a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, carboplatin and paclitaxel; and
  • a therapeutically effective amount of a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof is administered to the subject.
  • the first treatment phase comprises 1-14 treatment cycles, preferably 2-12 treatment cycles, 2-10 treatment cycles, more preferably 2-8 treatment cycles, for example: 2-8 treatment cycles, 3-8 treatment cycles, 4-8 treatment cycles, 2-7 treatment cycles, 3-7 treatment cycles, 4-7 treatment cycles, 2-6 treatment cycles, 3-6 treatment cycles, or 4-6 treatment cycles; most preferably 4-6 treatment cycles, for example: 4 treatment cycles, 5 treatment cycles, and/or 6 treatment cycles.
  • the first treatment phase comprises 4 treatment cycles. In some embodiments, the first treatment phase comprises 6 treatment cycles.
  • one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some embodiments, one treatment cycle is every 3 weeks.
  • the second treatment phase is after the first treatment phase. In some embodiments, the second treatment phase is continued from the end of the first treatment phase until the patient loses clinical benefit, the toxicity is unacceptable, the efficacy is evaluated as PD, or the investigator deems it inappropriate to continue the medication.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be administered simultaneously, sequentially and/or alternately. In some embodiments, in the method or use, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered sequentially. In some embodiments, in the method or use, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered simultaneously.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are each in the form of a pharmaceutical composition and administered sequentially.
  • the anti-PD-1 antibody or its antigen-binding fragment is administered first, and then the anti-TIM-3 antibody or its antigen-binding fragment is administered.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are each in the form of a pharmaceutical composition, and the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is first administered, and then the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is administered.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single preparation and administered simultaneously.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapeutic drug can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapeutic drug are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately. In some embodiments, in the method or use, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are administered sequentially.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are each in the form of a pharmaceutical composition and can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single formulation, and the single formulation, cisplatin and paclitaxel are each in the form of a pharmaceutical composition, which can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single formulation, and the single formulation, cisplatin and paclitaxel are each in the form of a pharmaceutical composition, which can be administered sequentially.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately. In some embodiments, in the method or use, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel are administered sequentially. In some embodiments, in the method or use, the anti-TIM-3 antibody or antigen-binding fragment thereof, the anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel are each in the form of a pharmaceutical composition, which can be administered simultaneously.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single formulation, and the single formulation, carboplatin and paclitaxel are each in the form of a pharmaceutical composition, which can be administered simultaneously, sequentially and/or alternately.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single formulation, and the single formulation, carboplatin and paclitaxel are each in the form of a pharmaceutical composition and are administered sequentially.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered in the same or different dosing regimens. In some embodiments, in the method or use, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered in different dosing regimens.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and the chemotherapeutic drug are administered in the same or different dosing regimens.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are administered in the same or different dosing regimens.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are administered in different dosing regimens.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are administered in the same or different dosing regimens. In some specific embodiments, in the method or use, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are administered in different dosing regimens.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In a specific embodiment, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time.
  • the anti-TIM-3 antibody or its antigen-binding fragment is administered at a dose of about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 700 mg, about 800 mg, about 900 mg, about 1000 mg, about 1100 mg, about 1200 mg, about 1300 mg, about 1400 mg, about 1500 mg, about 1600 mg, about 1700 mg or about 1800 mg, or a range formed by any of the above values.
  • the anti-TIM-3 antibody or its antigen-binding fragment is administered at a dose of about 1200 mg or about 1500 mg each time. In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment is administered at a dose of about 1200 mg each time.
  • the anti-TIM-3 antibody or its antigen-binding fragment is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of anti-TIM-3 antibody or its antigen-binding fragment. In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 1200-1500 mg of anti-TIM-3 antibody or its antigen-binding fragment.
  • the anti-TIM-3 antibody or its antigen-binding fragment is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks, each time at a dose of about 1200 mg or about 1500 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks, each time at a dose of about 1200 mg of the anti-TIM-3 antibody or antigen-binding fragment thereof.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In a specific embodiment, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of about 10 mg, about 50 mg, about 100 mg, about 120 mg, about 140 mg, about 160 mg, about 180 mg, about 200 mg, about 220 mg, about 240 mg, about 260 mg, about 280 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, or about 800 mg, or a range formed by any of the above values.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of about 200 mg each time.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of 10-800 mg, 50-500 mg, or 100-200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, each time at a dose of about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof. In some embodiments, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks, each time at a dose of about 200 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.
  • the cisplatin in the method or use, is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the method or use, the cisplatin is administered once every 3 weeks (q3w). In some embodiments, the cisplatin is administered at a dose of 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 each time.
  • the cisplatin is administered at a dose of about 30 mg/m 2 , about 32 mg/m 2 , about 35 mg/m 2 , about 37 mg/m 2 , about 40 mg/m 2 , about 45 mg/m 2 , about 48 mg/m 2 , about 50 mg/m 2 , about 52 mg/m 2 , about 54 mg/m 2 , about 56 mg/m 2 , about 60 mg/m 2 , about 65 mg/m 2 , about 70 mg/m 2 , about 75 mg/m 2 , about 80 mg/m 2 , about 90 mg/m 2 , or about 100 mg/m 2 , or a range formed by any of the above values.
  • the cisplatin is administered at a dose of 48-75 mg/m 2 each time. In some embodiments, the cisplatin is administered at a dose of 30-75 mg/m 2 each time. In some embodiments, the cisplatin is administered at a dose of 60-75 mg/m 2 each time. In some embodiments, the cisplatin is administered once every 3 weeks, each time at a dose of 48-75 mg/m 2 cisplatin. In some embodiments, the cisplatin is administered once every 3 weeks, each time at a dose of 30-75 mg/m 2 cisplatin.
  • the cisplatin is administered once every 3 weeks, each time at a dose of 60-75 mg/m 2 cisplatin. In some embodiments, the cisplatin is administered once every 3 weeks, each time at a dose of about 75 mg/m 2 cisplatin. In some embodiments, the cisplatin is administered once every 3 weeks, each time at a dose of about 60 mg/m 2 or about 75 mg/m 2 cisplatin.
  • the carboplatin in the method or use, is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the method or use, the carboplatin is administered once every 3 weeks (q3w). In some embodiments, the carboplatin is administered at a dose of 2.5-5mg/(mL/min)AUC or 3.2-5mg/(mL/min)AUC each time.
  • the carboplatin is administered at a dose of about 2.5mg/(mL/min)AUC, about 3mg/(mL/min)AUC, about 3.2mg/(mL/min)AUC, about 3.5mg/(mL/min)AUC, about 3.75mg/(mL/min)AUC, about 4mg/(mL/min)AUC, about 4.5mg/(mL/min)AUC, or about 5mg/(mL/min)AUC, or a range of carboplatin in the range of any of the above values.
  • the carboplatin is administered at a dose of 3.2-5 mg/(mL/min)AUC each time.
  • the carboplatin is administered at a dose of 5 mg/(mL/min)AUC each time. In some embodiments, the carboplatin is administered once every 3 weeks, each time at a dose of 3.2-5 mg/(mL/min)AUC. In some embodiments, the carboplatin is administered once every 3 weeks, each time at a dose of 5 mg/(mL/min)AUC.
  • the paclitaxel in the method or use, is administered once every 1 week (q1w), every 2 weeks (q2w), every 3 weeks (q3w), or every 4 weeks (q4w). In some embodiments, in the method or use, the paclitaxel is administered once every 3 weeks (q3w). In some embodiments, the paclitaxel is administered at a dose of 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 each time.
  • the paclitaxel is administered at a dose of about 75 mg/m 2 , about 90 mg/m 2 , about 100 mg/m 2 , about 105 mg/m 2 , about 109 mg/m 2 , about 112 mg/m 2 , about 135 mg/m 2 , about 140 mg/m 2 , about 145 mg/m 2 , about 150 mg/m 2 , or about 175 mg/m 2 , or a range formed by any of the above values.
  • the paclitaxel is administered at a dose of 112-175 mg/m 2.
  • the paclitaxel is administered at a dose of 67.5-150 mg/m 2.
  • the paclitaxel is administered at a dose of 135-150 mg/m 2 . In some embodiments, the paclitaxel is administered once every 3 weeks, each time at a dose of 112-175 mg/m 2 paclitaxel. In some embodiments, the paclitaxel is administered once every 3 weeks, each time at a dose of 67.5-150 mg/m 2 paclitaxel. In some embodiments, the paclitaxel is administered once every 3 weeks, each time at a dose of 135-150 mg/m 2 paclitaxel. In some embodiments, the paclitaxel is administered once every 3 weeks, each time at a dose of about 175 mg/m 2 paclitaxel. In some embodiments, the paclitaxel is administered once every 3 weeks, each time at a dose of about 135 mg/m 2 or about 150 mg/m 2 paclitaxel.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment have the same or different treatment cycles.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment have the same treatment cycle, for example, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment have the same treatment cycle, for example, one treatment cycle is every 3 weeks.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, and the chemotherapeutic drug have the same or different treatment cycles, respectively.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel have the same or different treatment cycles, respectively.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel have the same treatment cycle, for example, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. In some specific embodiments, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel have the same treatment cycle, for example, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks.
  • anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel have the same treatment cycle, for example, one treatment cycle is every 3 weeks.
  • anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel have the same or different treatment cycles respectively.
  • anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel have the same treatment cycle, for example, one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks.
  • anti-TIM-3 antibody or its antigen-binding fragment, anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel have the same treatment cycle, for example, one treatment cycle is every 3 weeks.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof are administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof are administered on the first day of each treatment cycle, and anti-PD-1 antibodies or antigen-binding fragments thereof are administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle
  • anti-TIM-3 antibodies or antigen-binding fragments thereof are administered once on the first day of each treatment cycle
  • anti-PD-1 antibodies or antigen-binding fragments thereof are administered once on the first day of each treatment cycle.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.
  • every 3 weeks is a treatment cycle, and the single formulation is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single formulation is administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single formulation is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single formulation is administered once on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle.
  • one treatment cycle is 3 weeks, and about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, and about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, and chemotherapy drugs are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, cisplatin and paclitaxel are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, carboplatin and paclitaxel are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, cisplatin and paclitaxel are administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and anti-TIM-3 antibodies or antigen-binding fragments thereof, anti-PD-1 antibodies or antigen-binding fragments thereof, carboplatin and paclitaxel are administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered on day 1 of each treatment cycle, an anti-PD-1 antibody or an antigen-binding fragment thereof is administered on day 1 of each treatment cycle, cisplatin or carboplatin is administered on day 1 of each treatment cycle, and paclitaxel is administered on day 1 of each treatment cycle.
  • every 3 weeks is a treatment cycle
  • an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle
  • an anti-PD-1 antibody or an antigen-binding fragment thereof is administered once on day 1 of each treatment cycle
  • cisplatin or carboplatin is administered once on day 1 of each treatment cycle
  • paclitaxel is administered once on day 1 of each treatment cycle.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.
  • every 3 weeks is a treatment cycle, and the single formulation and chemotherapy drugs are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single formulation, cisplatin and paclitaxel are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single formulation, cisplatin and paclitaxel are administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single preparation, cisplatin and paclitaxel are each administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single preparation, carboplatin and paclitaxel are each administered once in each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single preparation is administered on Day 1 of each treatment cycle, cisplatin or carboplatin is administered on Day 1 of each treatment cycle, and paclitaxel is administered on Day 1 of each treatment cycle.
  • every 3 weeks is a treatment cycle, and the single preparation is administered once on Day 1 of each treatment cycle, cisplatin or carboplatin is administered once on Day 1 of each treatment cycle, and paclitaxel is administered once on Day 1 of each treatment cycle.
  • every 3 weeks is a treatment cycle, and 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered in each treatment cycle, 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 of cisplatin is administered in each treatment cycle, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 48-75 mg/m 2 of cisplatin is administered in each treatment cycle, and 112-175 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 75 mg/m 2 of cisplatin is administered in each treatment cycle, and 175 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, and about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 30-75 mg/m 2 of cisplatin is administered in each treatment cycle, and 67.5-150 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 60-75 mg/m 2 of cisplatin is administered in each treatment cycle, and 135-150 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 60-75 mg/m 2 of cisplatin is administered in each treatment cycle, and 135-150 mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 48-75 mg/m 2 of cisplatin is administered on the first day of each treatment cycle, and 112-175 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 75 mg/m 2 of cisplatin is administered on the first day of each treatment cycle, and 175 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 60-75 mg/m 2 of cisplatin is administered on the first day of each treatment cycle, and 135-150 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 60-75 mg/m 2 of cisplatin is administered on the first day of each treatment cycle, and 135-150 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 60 mg/m 2 or about 75 mg/m 2 of cisplatin is administered on the first day of each treatment cycle, and about 135 mg/m 2 or about 150 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, and in each treatment cycle, 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof is administered, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof is administered, 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC of carboplatin is administered in each treatment cycle, and 75-175 mg/m 2 , 100-175 mg/m 2 , or 100-1500 mg of anti-PD-1 antibody or an antigen-binding fragment thereof is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200mg or about 1500mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 3.2-5mg/(mL/min)AUC of carboplatin is administered in each treatment cycle, and 112-175mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200mg of anti-TIM-3 antibody or its antigen-binding fragment is administered in each treatment cycle, about 200mg of anti-PD-1 antibody or its antigen-binding fragment is administered in each treatment cycle, 5mg/(mL/min)AUC of carboplatin is administered in each treatment cycle, and 175mg/m 2 of paclitaxel is administered in each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg or about 1500 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 3.2-5 mg/(mL/min) AUC of carboplatin is administered on the first day of each treatment cycle, and 112-175 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • every 3 weeks is a treatment cycle, about 1200 mg of anti-TIM-3 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, about 200 mg of anti-PD-1 antibody or its antigen-binding fragment is administered on the first day of each treatment cycle, 5 mg/(mL/min) AUC of carboplatin is administered on the first day of each treatment cycle, and 175 mg/m 2 of paclitaxel is administered on the first day of each treatment cycle.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1 of the anti-TIM-3 antibody or its antigen-binding fragment: the anti-PD-1 antibody or its antigen-binding fragment; optionally, the subject is further administered a chemotherapeutic drug.
  • the chemotherapeutic drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug.
  • the chemotherapeutic drug is cisplatin and paclitaxel. In other specific embodiments, the chemotherapeutic drug is carboplatin and paclitaxel.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of anti-TIM-3 antibody or its antigen-binding fragment: anti-PD-1 antibody or its antigen-binding fragment of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1; optionally, the subject is further administered cisplatin and paclitaxel.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered to the subject at a mass ratio of anti-TIM-3 antibody or its antigen-binding fragment: anti-PD-1 antibody or its antigen-binding fragment of (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1; optionally, the subject is further administered carboplatin and paclitaxel.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered in multiple doses or a single dose. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are administered in multiple doses. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment and the chemotherapeutic drug are administered in multiple doses or a single dose.
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are administered in multiple doses or a single dose. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, cisplatin and paclitaxel are administered in multiple doses. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are administered in multiple doses or a single dose. In some embodiments, in each treatment cycle, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, carboplatin and paclitaxel are administered in multiple doses.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof can be selected from 0.01 to 50 mg/kg, 0.1 to 40 mg/kg, 0.1 to 35 mg/kg, 0.1 to 30 mg/kg, 0.1 to 25 mg/kg, 0.1 to 20 mg/kg, 0.1 to 15 mg/kg, 0.1 to 10 mg/kg, 1 to 40 mg/kg, 1 to 35 mg/kg, 1 to 30 mg/kg, 1 to 25 mg/kg, 1 to 20 mg/kg, 1 to 15 mg/kg, 1 to 10 mg/kg, 1 to 3 mg/kg, 3 to 40 mg/kg, 3 to 35 mg/kg, 3 to 30 mg/kg, 3 to 25 mg/kg, 3 to 20 mg/kg, 3 to 15 mg/kg, 3 to 10 mg/kg, 10 to 40 mg/kg, 10 to 30 mg/kg, 10 to 2 5 mg/kg, or 20 to 25 mg/kg; or 1-2400 mg, 20-1800 mg, 100-1800 mg, 300-1800 mg, 600-1600 mg, 700
  • the anti-PD-1 antibody or antigen-binding fragment thereof can be selected from 0.01 to 50 0.1 to 40 mg/kg, 0.1 to 35 mg/kg, 0.1 to 30 mg/kg, 0.1 to 25 mg/kg, 0.1 to 20 mg/kg, 0.1 to 15 mg/kg, 0.1 to 10 mg/kg, 1 to 30 mg/kg, 1 to 25 mg/kg, 1 to 20 mg/kg, 1 to 15 mg/kg, 1 to 10 mg/kg, 1 to 8 mg/kg, 1 to 5 mg/kg, 1 to 3 mg/kg, 3 to 30 mg/kg, 3 to 25 mg/kg, 3 to 20 mg/kg, 3 to 15 mg/kg, 3 to 10 mg/kg, 3 to 8mg/kg, or 3 to 5mg/kg; or administered to a subject at a uniform dose of 1-1000mg, 10-1000mg, 10-800mg, 20-800mg, 40-800mg, 50-700mg, 50-600mg, 50-500mg, 60
  • the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment, the chemotherapy drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel) dosage regimen (e.g., dosing cycle, dosage and dosage adjustment) can be adjusted according to the severity of the disease, the response of the disease, any treatment-related toxicity, the age and health status of the patient.
  • a treatment cycle of anti-TIM-3 antibody or its antigen-binding fragment and/or anti-PD-1 antibody or its antigen-binding fragment can be adjusted to 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks or 15 weeks.
  • the dosage of cisplatin, carboplatin and/or paclitaxel can be adjusted to 80%, 75% or 64% of the initial dosage.
  • a treatment cycle of cisplatin, carboplatin and/or paclitaxel can be adjusted to 4 weeks.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises: a heavy chain CDR1 (HCDR1) of the amino acid sequence shown in SEQ ID NO: 1 or 21, a HCDR2 of the amino acid sequence shown in SEQ ID NO: 2 or 22, a HCDR3 of the amino acid sequence shown in SEQ ID NO: 3 or 23, a light chain CDR1 (LCDR1) of the amino acid sequence shown in SEQ ID NO: 4 or 24, a LCDR2 of the amino acid sequence shown in SEQ ID NO: 5 or 25, and a LCDR3 of the amino acid sequence shown in SEQ ID NO: 6 or 26.
  • HCDR1 heavy chain CDR1
  • LCDR1 light chain CDR1
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 1, HCDR2 of the amino acid sequence shown in SEQ ID NO: 2, HCDR3 of the amino acid sequence shown in SEQ ID NO: 3, LCDR1 of the amino acid sequence shown in SEQ ID NO: 4, LCDR2 of the amino acid sequence shown in SEQ ID NO: 5, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 6.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 21, HCDR2 of the amino acid sequence shown in SEQ ID NO: 22, HCDR3 of the amino acid sequence shown in SEQ ID NO: 23, LCDR1 of the amino acid sequence shown in SEQ ID NO: 24, LCDR2 of the amino acid sequence shown in SEQ ID NO: 25, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 26.
  • the CDR sequences of anti-TIM-3 antibodies or antigen-binding fragments thereof are shown in Table 1.
  • CDR complementarity determining region
  • Table 1 shows CDR sequences (wherein the CDR regions shown in SEQ ID NO: 1-6 are defined by the AbM numbering system), however, when referring to antibodies defined by specific CDR sequences defined by certain divisions, the scope of the antibodies also covers antibodies defined by CDR sequences converted to other arbitrary numbering system definitions (e.g., a combination of one or more of the Kabat, Chothia, IMGT, CCG or Contact definitions known in the art).
  • an anti-TIM-3 antibody or an antigen-binding fragment thereof comprising the following amino acid sequences is also covered within the scope of the anti-TIM-3 antibody or an antigen-binding fragment thereof of the present disclosure: HCDR1 of the amino acid sequence shown in SEQ ID NO:1, HCDR2 of the amino acid sequence shown in SEQ ID NO:2, HCDR3 of the amino acid sequence shown in ARRYYGYDAMDY (SEQ ID NO:31), LCDR1 of the amino acid sequence shown in SEQ ID NO:4, LCDR2 of the amino acid sequence shown in SEQ ID NO:5, and LCDR3 of the amino acid sequence shown in SEQ ID NO:6.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises an amino acid sequence similar to that shown in SEQ ID NO: 7 or 27.
  • the amino acid sequence has a heavy chain variable region that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region whose amino acid sequence is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 8 or 28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 7.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain variable region of the amino acid sequence shown in SEQ ID NO: 8.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:7 or 27, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO:8 or 28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 7, and a light chain variable region of the amino acid sequence shown in SEQ ID NO: 8.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 27, and a light chain variable region of the amino acid sequence shown in SEQ ID NO: 28.
  • the amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 7, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 8.
  • the amino acid sequence of the heavy chain variable region of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 27, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 28.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 1, HCDR2 comprises the amino acid sequence of SEQ ID NO: 2, HCDR3 comprises the amino acid sequence of SEQ ID NO: 3, LCDR1 comprises the amino acid sequence of SEQ ID NO: 4, LCDR2 comprises the amino acid sequence of SEQ ID NO: 5, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 6, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:8.
  • the anti-TIM-3 antibody or its antigen-binding fragment may also include a constant region of an immunoglobulin, or a fragment, analog, variant or derivative of the constant region.
  • the heavy chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG4 heavy chains.
  • the light chain constant region is from a human immunoglobulin light chain, such as a ⁇ light chain or a ⁇ light chain of a human immunoglobulin.
  • the constant region may include modifications described in any text, such as insertion, deletion, substitution or chemical modification of amino acids.
  • the constant region includes mutations that change effector function.
  • any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 9.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence as shown in SEQ ID NO: 10.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 9 or 29, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 10 or 30.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain of the amino acid sequence shown in SEQ ID NO: 9, and a light chain of the amino acid sequence shown in SEQ ID NO: 10. In some embodiments, the anti-TIM-3 antibody or antigen-binding fragment thereof comprises a heavy chain of the amino acid sequence shown in SEQ ID NO: 29, and a light chain of the amino acid sequence shown in SEQ ID NO: 30. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 9, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 10. In some specific embodiments, the amino acid sequence of the heavy chain of the anti-TIM-3 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 29, and the amino acid sequence of the light chain is as shown in SEQ ID NO: 30.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein is mAb 50B5 or an antigen-binding fragment thereof described in the patent application document with publication number WO2020041520 or CN112566936, or a chimeric antibody or an antigen-binding fragment thereof of mAb 50B5, or a humanized antibody or an antigen-binding fragment thereof of mAb 50B5.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof disclosed herein is mAb 15B4 or an antigen-binding fragment thereof described in the patent application document with publication number WO2020041520 or CN112566936, or a chimeric antibody or an antigen-binding fragment thereof of mAb 15B4, or a humanized antibody or an antigen-binding fragment thereof of mAb 15B4.
  • the anti-TIM-3 antibody or antigen-binding fragment thereof of the present invention is selected from Sabatolimab, Cobolimab, Surzebiclimab, Roche's Lomvastomig (RG-7769), Hengrui Medicine's SHR-1702, Agenus' Verzistobart (INCAGN-2390), WuXi Biologics' BC-3402, Wellizhibo's LBL-003, Jianxin Bio's LNL-005, or BMS's BMS-986258.
  • the anti-PD-1 antibody or antigen-binding fragment thereof described in the present disclosure comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO: 11, HCDR2 of the amino acid sequence shown in SEQ ID NO: 12, HCDR3 of the amino acid sequence shown in SEQ ID NO: 13, LCDR1 of the amino acid sequence shown in SEQ ID NO: 14, LCDR2 of the amino acid sequence shown in SEQ ID NO: 15, and LCDR3 of the amino acid sequence shown in SEQ ID NO: 16.
  • the CDR sequences of the anti-PD-1 antibody or antigen-binding fragment thereof are shown in Table 2.
  • CDR complementarity determining region
  • a given antibody or region thereof e.g., variable region
  • CDR regions have been shown in Table 2, however, when referring to antibodies defined by specific CDR sequences defined by certain divisions, the scope of the antibodies also encompasses antibodies defined by CDR sequences converted to other arbitrary numbering system definitions (e.g., a combination of one or more of the definitions of AbM, Kabat, Chothia, IMGT, CCG or Contact, etc., known in the art).
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 17.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region of the amino acid sequence shown in SEQ ID NO: 17.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain variable region of the amino acid sequence shown in SEQ ID NO: 18.
  • the anti-PD-1 antibody or its antigen-binding fragment comprises a heavy chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:17, and a light chain variable region having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identical to the amino acid sequence shown in SEQ ID NO:18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence as shown in SEQ ID NO: 18.
  • the amino acid sequence of the heavy chain variable region of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 17, and the amino acid sequence of the light chain variable region is as shown in SEQ ID NO: 18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof described in the present disclosure comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3, wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, HCDR3 comprises the amino acid sequence of SEQ ID NO: 13, LCDR1 comprises the amino acid sequence of SEQ ID NO: 14, LCDR2 comprises the amino acid sequence of SEQ ID NO: 15, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 16, and the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 17.
  • NO:17 has an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical
  • the light chain variable region comprises an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO:18.
  • the anti-PD-1 antibody or antigen-binding fragment thereof may further comprise an immunoglobulin constant region, or a fragment, analog, variant or derivative of the constant region.
  • the heavy chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG1 heavy chains.
  • the light chain constant region is from a human immunoglobulin heavy chain, such as IgG1, IgG2, IgG3 and IgG4 or other classes of immunoglobulin heavy chains, preferably IgG1 heavy chains.
  • the constant region is from a human immunoglobulin light chain, such as a kappa light chain or a lambda light chain of a human immunoglobulin.
  • the constant region may include any modification described in the text, such as insertion, deletion, substitution or chemical modification of amino acids.
  • the constant region includes mutations that alter effector function.
  • any amino acid residue in the constant region may be substituted with an amino acid residue of any allotype.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 19.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain having an amino acid sequence at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain of the amino acid sequence shown in SEQ ID NO: 19.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a light chain of the amino acid sequence shown in SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19, and a light chain having an amino acid sequence that is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20.
  • the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 19, and a light chain having an amino acid sequence as shown in SEQ ID NO: 20.
  • the heavy chain amino acid sequence of the anti-PD-1 antibody or antigen-binding fragment thereof is as shown in SEQ ID NO: 19, and the light chain amino acid sequence is as shown in SEQ ID NO: 20.
  • the anti-PD-1 antibodies or antigen-binding fragments thereof disclosed herein are selected from nivolumab, pembrolizumab, toripalimab, sintilimab, camrelizumab, tislelizumab, zimberelimab, balstilimab, geptanolimab, Lipustobart (LZM-1) of Livzon Pharmaceuticals, and the like.
  • composition containing antibody or antigen-binding fragment thereof
  • the anti-TIM-3 antibody or its antigen-binding fragment and/or the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for parenteral administration.
  • the anti-TIM-3 antibody or its antigen-binding fragment and/or the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for intravenous, intramuscular, subcutaneous or other parenteral administration, for example, for injection or infusion. In some specific embodiments, for intravenous, intramuscular or subcutaneous administration. In some specific embodiments, for intravenous injection or infusion.
  • Anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof can be formulated into suitable dosage forms, including but not limited to tablets, lozenges, pills, capsules (e.g., hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (i.e., preparations suitable for injection, such as preparations suitable for intramuscular, intravenous, intraperitoneal, subcutaneous injections), granules, emulsions, suspensions.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be formulated into an injection.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be formulated into a preparation suitable for intravenous injection.
  • the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated in a single formulation. In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment, the anti-PD-1 antibody or its antigen-binding fragment are formulated together with one or more pharmaceutically acceptable carriers to prepare a suitable pharmaceutical composition.
  • the anti-TIM-3 antibody or its antigen-binding fragment is formulated separately from the anti-PD-1 antibody or its antigen-binding fragment (ie, each in the form of a pharmaceutical composition). In some embodiments, the anti-TIM-3 antibody or its antigen-binding fragment is formulated together with one or more pharmaceutically acceptable carriers to prepare a suitable pharmaceutical composition. In some embodiments, the anti-PD-1 antibody or its antigen-binding fragment is formulated together with one or more pharmaceutically acceptable carriers to prepare a suitable pharmaceutical composition.
  • Pharmaceutically acceptable carriers include, for example, excipients, diluents, encapsulating materials, fillers, buffers or other agents.
  • the unit dose of the pharmaceutical composition containing the anti-TIM-3 antibody or its antigen-binding fragment is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg of the anti-TIM-3 antibody or its antigen-binding fragment, for example, about 60 mg, about 120 mg, about 160 mg, about 180 mg, about 200 mg, about 240 mg, about 280 mg, about 300 mg, about 320 mg, about 360 mg, about 400 mg, about 420 mg, about 440 mg, about 480 mg, about 520 mg, about 540 mg, about 560 mg, about 600 mg, about 640 mg, about 660 mg, about 680 mg, about 720 mg, about 760 mg, about 780 mg, about 800 mg, about 8 1500 mg, about 1520 mg, about 1560 mg, about 1600 mg, about 1620 mg, about 1640 mg, about 1680 mg, about 1720 mg, about 1740 mg, about 1760 mg and/or about 1800 mg, or a range formed by any of the fore
  • the unit dose of the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg of the anti-PD-1 antibody or its antigen-binding fragment, for example, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 70 mg, about 80 mg, about 90 mg, about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about about 450 mg, about 460 mg, about 470 mg, about 480 mg, about 490 mg and/or about 500 mg, or a range formed by any of the foregoing values.
  • the pharmaceutical composition containing anti-TIM-3 antibody or antigen-binding fragment thereof is a water-soluble injection.
  • the pharmaceutical composition containing anti-PD-1 antibody or antigen-binding fragment thereof is a water-soluble injection.
  • the pharmaceutical composition containing anti-TIM-3 antibody or antigen-binding fragment thereof and anti-PD-1 antibody or antigen-binding fragment thereof is a water-soluble injection.
  • the water-soluble injection includes but is not limited to a water-soluble preparation that has not been lyophilized or a water-soluble preparation reconstituted with a lyophilized powder.
  • the pharmaceutical composition containing anti-TIM-3 antibodies or antigen-binding fragments thereof is a lyophilized preparation. In other embodiments, the pharmaceutical composition containing anti-PD-1 antibodies or antigen-binding fragments thereof is a lyophilized preparation. In a specific embodiment, the pharmaceutical composition containing anti-TIM-3 antibodies or antigen-binding fragments thereof and anti-PD-1 antibodies or antigen-binding fragments thereof is a lyophilized preparation.
  • the lyophilized preparation refers to a preparation prepared by a freeze-drying process of an aqueous solution, in which the substance is first frozen, and then the amount of solvent is reduced by sublimation (primary drying process), and then the amount of solvent is reduced by desorption (secondary drying process) until the amount of solvent is a value that no longer supports biological activity or chemical reaction.
  • the lyophilized preparation of the present disclosure can also be dried by other methods known in the art, such as spray drying and bubble drying.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment in the pharmaceutical composition containing the anti-PD-1 antibody or its antigen-binding fragment is 0.1-50 mg/mL, 0.5-30 mg/mL, 0.8-20 mg/mL, 1-15 mg/mL, 1-10 mg/mL, 1-5 mg/mL, 2-20 mg/mL, 2-15 mg/mL, 2-10 mg/mL, or 2-5 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is about 0.8 mg/mL, about 1 mg/mL, about 2 mg/mL, about 3 mg/mL, about 4 mg/mL, about 5 mg/mL, about 6 mg/mL, about 7 mg/mL, about 8 mg/mL, about 9 mg/mL, about 10 mg/mL, about 15 mg/mL, or about 20 mg/mL.
  • the concentration of the anti-PD-1 antibody or its antigen-binding fragment is about 1 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 2 mg/mL. In some embodiments, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 5 mg/mL. In one embodiment, the concentration of the anti-PD-1 antibody or antigen-binding fragment thereof is about 10 mg/mL.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is in the form of a pharmaceutical composition, which comprises an anti-PD-1 antibody or antigen-binding fragment thereof, a buffer, an isotonicity regulator/stabilizer, and a surfactant.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is in the form of a liquid preparation (e.g., an injection), which comprises an anti-PD-1 antibody or antigen-binding fragment thereof, sodium acetate trihydrate, glacial acetic acid, sorbitol, and polysorbate 80.
  • the chemotherapy drugs are not limited to platinum anti-tumor drugs (including but not limited to oxaliplatin, cisplatin, carboplatin, nedaplatin, dicycloplatin, miplatin, lobaplatin, picoplatin, Lobaplatin, triplatin tetranitrate, phenanthridine, satraplatin), camptothecin anti-tumor drugs (including but not limited to camptothecin, hydroxycamptothecin, aminocamptothecin, irinotecan, topotecan, exitecan, rubitecan, lurtotecan, gimatecan, karenitecin, 7-ethyl Camptothecin), taxane anti-tumor drugs (including but not limited to paclitaxel and docetaxel), nitrogen mustard anti-tumor drugs (including but not limited to cyclophosphamide, ifosfamide, chlorambucil,
  • the chemotherapy drug is selected from one or more of platinum anti-tumor drugs, taxane anti-tumor drugs, and antimetabolite anti-tumor drugs. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug. In some embodiments, the chemotherapy drug is a platinum anti-tumor drug and a taxane anti-tumor drug.
  • the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin, preferably carboplatin and/or cisplatin, more preferably cisplatin.
  • the taxane anti-tumor drugs include various components having the taxane skeleton isolated from Taxus brevifolia or their semi-synthetic products, or pure synthetic products having the taxane skeleton. Specifically, they include paclitaxel, cabazitaxel, docetaxel, etc., preferably paclitaxel. Among them, paclitaxel includes but is not limited to paclitaxel injection, paclitaxel lyophilized powder, paclitaxel liposomes and albumin-bound paclitaxel, etc.
  • the chemotherapy drugs are cisplatin and paclitaxel. In some specific embodiments, the chemotherapy drugs are carboplatin and paclitaxel.
  • the chemotherapy drug is administered according to a known administration regimen (including administration cycle, administration dosage and dosage adjustment, and administration route).
  • the unit dose of the pharmaceutical composition containing cisplatin is 2.5 mg, 5 mg, 10 mg, 20 mg, 25 mg, 30 mg, 50 mg and/or 100 mg of cisplatin. In some embodiments, the unit dose of the pharmaceutical composition containing cisplatin is 10 mg, 20 mg, 30 mg, 50 mg and/or 100 mg of cisplatin.
  • the unit dose of the pharmaceutical composition containing carboplatin is 50 mg, 100 mg, 150 mg, 250 mg and/or 450 mg.
  • the unit dose of the pharmaceutical composition containing paclitaxel is 30 mg, 60 mg, 100 mg and/or 150 mg of paclitaxel.
  • the pharmaceutical composition containing cisplatin is a preparation suitable for injection. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid preparation. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid preparation suitable for injection. In some embodiments, the pharmaceutical composition containing cisplatin is a liquid preparation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing cisplatin is a solid preparation. In some embodiments, the pharmaceutical composition containing cisplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing cisplatin is a powder injection preparation. Suitable preparations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, the pharmaceutically acceptable carrier of the liquid preparation containing cisplatin suitable for injection includes polyethylene glycol 400 and sodium chloride.
  • the pharmaceutical composition containing carboplatin is a preparation suitable for injection. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid preparation. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid preparation suitable for injection. In some embodiments, the pharmaceutical composition containing carboplatin is a liquid preparation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing carboplatin is a solid preparation. In some embodiments, the pharmaceutical composition containing carboplatin is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing carboplatin is a powder injection preparation. Suitable preparations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, the pharmaceutically acceptable carrier of the liquid preparation containing carboplatin suitable for injection includes water for injection. In a specific embodiment, the pharmaceutically acceptable carrier of the solid preparation containing carboplatin suitable for injection includes mannitol.
  • the pharmaceutical composition containing paclitaxel is a preparation suitable for injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid preparation. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid preparation suitable for injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a liquid preparation suitable for intravenous injection. In some embodiments, the pharmaceutical composition containing paclitaxel is a solid preparation. In some embodiments, the pharmaceutical composition containing paclitaxel is a lyophilized preparation. In some specific embodiments, the pharmaceutical composition containing paclitaxel is a powder injection preparation. Suitable preparations can be prepared by conventional methods using pharmaceutically acceptable carriers known in the art. In a specific embodiment, the pharmaceutically acceptable carrier of the liquid preparation containing paclitaxel suitable for injection includes polyoxyethylene castor oil and anhydrous ethanol.
  • each component in the drug combination of the present disclosure can be administered independently or partly or all thereof together in various suitable routes, including but not limited to parenteral (e.g., by intravenous, intramuscular, topical or subcutaneous routes).
  • parenteral e.g., by intravenous, intramuscular, topical or subcutaneous routes.
  • each component of the drug combination of the present disclosure can be administered independently or partly or all thereof together by injection, such as intravenous or subcutaneous injection.
  • the components in the pharmaceutical combination of the present disclosure can be independently or partially or all of them are formulated into suitable dosage forms, including but not limited to tablets, lozenges, pills, capsules (e.g., hard capsules, soft capsules, enteric-coated capsules, microcapsules), elixirs, granules, syrups, injections (i.e., preparations suitable for injection, such as preparations suitable for intramuscular, intravenous, intraperitoneal, subcutaneous injections), granules, emulsions, suspensions, solutions, dispersants, and sustained-release preparations for oral or parenteral administration.
  • the components of the pharmaceutical combination of the present disclosure can be independently or partially or all of them are formulated into injections.
  • the pharmaceutical combination of the present disclosure may further comprise an additional therapeutic agent.
  • the additional therapeutic agent may be a tumor therapeutic agent known in the art.
  • the tumor described in the present disclosure is a malignant tumor (ie, cancer); the malignant tumor refers to any malignant and/or invasive growth caused by abnormal cell growth.
  • the tumor is a solid tumor. In some embodiments, the tumor is a newly treated, unresectable, refractory, advanced, recurrent and/or metastatic solid tumor. In some embodiments, the tumor is an unresectable solid tumor. In some embodiments, the tumor is an advanced solid tumor. In some embodiments, the tumor is a locally advanced solid tumor. In some embodiments, the tumor is a recurrent and/or metastatic solid tumor. In some embodiments, the tumor is a locally advanced, recurrent or metastatic solid tumor. In some embodiments, the tumor is an unresectable, recurrent or metastatic solid tumor.
  • the tumor is head and neck cancer. In some embodiments, the tumor is head and neck cancer without local radical treatment indications. In some embodiments, the tumor is a newly treated, unresectable, refractory, advanced, recurrent and/or metastatic head and neck cancer. In some embodiments, the tumor is an unresectable head and neck cancer. In some embodiments, the tumor is an advanced head and neck cancer. In some embodiments, the tumor is a locally advanced head and neck cancer. In some embodiments, the tumor is a recurrent and/or metastatic head and neck cancer. In some embodiments, the tumor is a locally advanced, recurrent or metastatic head and neck cancer without local radical treatment indications. In some embodiments, the tumor is an unresectable, recurrent or metastatic head and neck cancer without local radical treatment indications.
  • the head and neck cancer described in the present disclosure is a type of cancer that mainly starts in the lips, oral cavity, salivary glands, pharynx, larynx, nasal cavity and paranasal sinuses, including but not limited to external nose-nasal cavity tumors, paranasal sinus tumors, lip and oral cavity tumors, oropharyngeal tumors, hypopharyngeal tumors, laryngeal tumors, cervical trachea, esophageal tumors, thyroid tumors, salivary gland tumors, cervical lymph node metastasis, skin and appendage tumors.
  • the head and neck cancer includes but is not limited to oral tumors, oropharyngeal tumors, hypopharyngeal tumors and laryngeal tumors. In some embodiments, the head and neck cancer includes but is not limited to nasal tumors. Cavity and sinus tumors.
  • the head and neck cancer described in the present disclosure includes squamous cell carcinoma (abbreviated as SCC), basal cell carcinoma, adenoid cystic carcinoma, papillary carcinoma, follicular carcinoma, medullary carcinoma, undifferentiated carcinoma, etc.
  • the head and neck cancer is head and neck squamous cell carcinoma (abbreviated as HNSCC).
  • the tumor is a metastatic head and neck squamous cell carcinoma with the lip, oral cavity, salivary gland, pharynx, larynx, nasal cavity and paranasal sinuses as primary sites. In some embodiments, the tumor is a metastatic head and neck squamous cell carcinoma with the oral cavity, oropharynx, hypopharynx and larynx as primary sites. In some embodiments, the tumor is a metastatic head and neck squamous cell carcinoma with the nasal cavity and paranasal sinuses as primary sites.
  • the head and neck cancer does not include nasopharyngeal carcinoma. In some embodiments, the head and neck squamous cell carcinoma does not include nasopharyngeal carcinoma.
  • the tumor is a head and neck squamous cell carcinoma with no local radical treatment indication.
  • the tumor is a newly treated, unresectable, refractory, advanced, recurrent and/or metastatic head and neck squamous cell carcinoma.
  • the tumor is an unresectable head and neck squamous cell carcinoma.
  • the tumor is an advanced head and neck squamous cell carcinoma.
  • the tumor is a locally advanced head and neck squamous cell carcinoma.
  • the tumor is a recurrent and/or metastatic head and neck squamous cell carcinoma.
  • the tumor is a locally advanced, recurrent or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is an unresectable, recurrent or metastatic head and neck squamous cell carcinoma. In some embodiments, the tumor is a recurrent or metastatic head and neck squamous cell carcinoma with no local radical treatment indication. In some embodiments, the tumor is a locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no local radical treatment indication. In some embodiments, the tumor is an unresectable, recurrent or metastatic head and neck squamous cell carcinoma with no local radical treatment indication.
  • the subject of the head and neck squamous cell carcinoma has not been previously treated for head and neck squamous cell carcinoma (e.g., lack of an effective treatment regimen).
  • the subject of the head and neck squamous cell carcinoma has not previously received radiotherapy, chemotherapy, and/or immunotherapy to treat head and neck squamous cell carcinoma.
  • the subject of the head and neck squamous cell carcinoma has not previously received systemic treatment to treat head and neck squamous cell carcinoma.
  • the subject of the head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • immune checkpoint e.g., PD-1, PD-L1, CTLA-4 or TIM-3 inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma without local radical treatment indication has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • the subject of the first-line, unresectable, refractory, advanced, recurrent and/or metastatic head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • the subject of the unresectable head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • the subject of the advanced head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • the subject of the locally advanced head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject of the recurrent and/or metastatic head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject of the recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indication has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received systemic treatment for head and neck squamous cell carcinoma. In some embodiments, the subject with unresectable, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the newly treated, unresectable, refractory, advanced, recurrent and/or metastatic head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the unresectable head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the advanced head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the locally advanced head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the recurrent and/or metastatic head and neck squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject of the locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat head and neck squamous cell carcinoma.
  • the subject with unresectable, recurrent or metastatic head and neck squamous cell carcinoma who is not an indication for local radical treatment has not previously received an immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitor to treat head and neck squamous cell carcinoma.
  • an immune checkpoint e.g., PD-1, PD-L1, CTLA-4 or TIM-3 inhibitor to treat head and neck squamous cell carcinoma.
  • the subject of the head and neck squamous cell carcinoma has previously been treated with one or more different anti-tumor therapies for head and neck squamous cell carcinoma. Cancer.
  • the subject of head and neck squamous cell carcinoma has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma has not previously received systemic chemotherapy, but has received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat head and neck squamous cell carcinoma.
  • the subject of head and neck squamous cell carcinoma has achieved complete remission or partial remission after surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy, and the disease progresses again.
  • the subject of head and neck squamous cell carcinoma has metastasized after surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy.
  • the subject of head and neck squamous cell carcinoma has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma, and disease progression occurs 6 months (e.g., 6, 7, 8, 9 or 10 months) after stopping treatment.
  • the subject of head and neck squamous cell carcinoma has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma, and cancer metastasis occurs 6 months (e.g., 6, 7, 8, 9 or 10 months) after stopping treatment.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously been treated for head and neck squamous cell carcinoma with one or more different anti-tumor treatment methods.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has not previously received systemic chemotherapy, but has received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy to treat head and neck squamous cell carcinoma.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has recurred disease progression after complete remission or partial remission after surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has undergone surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma.
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and disease progression occurs 6 months after cessation of treatment (e.g., 6, 7, 8, 9 or 10 months).
  • the subject of locally advanced, recurrent and/or metastatic head and neck squamous cell carcinoma without local radical treatment indications has previously received surgery, radiotherapy, induction chemotherapy, concurrent chemotherapy and/or adjuvant chemotherapy for the treatment of head and neck squamous cell carcinoma, and cancer metastases 6 months after cessation of treatment (e.g., 6, 7, 8, 9 or 10 months).
  • the tumor is esophageal cancer. In some embodiments, the tumor is a newly treated, unresectable, refractory, recurrent, metastatic and/or advanced esophageal cancer. In some embodiments, the tumor is a newly treated esophageal cancer. In some embodiments, the tumor is an unresectable esophageal cancer. In some embodiments, the tumor is an advanced esophageal cancer. In some embodiments, the tumor is a locally advanced esophageal cancer. In some embodiments, the tumor is a recurrent and/or metastatic esophageal cancer. In some embodiments, the tumor is a locally advanced, recurrent or metastatic esophageal cancer. In some embodiments, the tumor is an unresectable, locally advanced, recurrent or metastatic esophageal cancer.
  • the esophageal cancer is esophageal squamous cell carcinoma (i.e., esophageal squamous cell carcinoma), esophageal adenocarcinoma, squamous cell carcinoma across the esophagogastric junction, or adenocarcinoma of the esophageal gastric junction.
  • the esophageal cancer is esophageal squamous cell carcinoma or esophageal adenocarcinoma.
  • the esophageal cancer is a newly treated esophageal squamous cell carcinoma.
  • the tumor is unresectable esophageal squamous cell carcinoma. In some embodiments, the tumor is advanced esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced esophageal squamous cell carcinoma. In some embodiments, the tumor is recurrent and/or metastatic esophageal squamous cell carcinoma. In some embodiments, the tumor is locally advanced, recurrent or metastatic esophageal squamous cell carcinoma. In some embodiments, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
  • the subject of the esophageal cancer has not been previously treated for esophageal cancer (e.g., lack of an effective treatment regimen). In some embodiments, the subject of the esophageal cancer has not previously received radiotherapy, chemotherapy, and/or immunotherapy to treat esophageal cancer. In some embodiments, the subject of the esophageal cancer has not previously received systemic therapy to treat esophageal cancer. In some embodiments, the subject of the esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • immune checkpoint e.g., PD-1, PD-L1, CTLA-4, or TIM-3
  • the subject with treatment-na ⁇ ve esophageal cancer has not previously received systemic therapy for esophageal cancer.
  • the subject with unresectable esophageal cancer has not previously received systemic therapy for esophageal cancer.
  • the subject with locally advanced esophageal cancer has not previously received systemic treatment for esophageal cancer.
  • the subject with locally advanced esophageal cancer has not previously received systemic treatment for esophageal cancer.
  • the subject with recurrent and/or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer.
  • the subject with locally advanced, recurrent or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer. In some embodiments, the subject with unresectable, locally advanced, recurrent or metastatic esophageal cancer has not previously received systemic treatment for esophageal cancer.
  • the subject of the first-line esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the unresectable esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the late esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the locally advanced esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the recurrent and/or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the locally advanced, recurrent, or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the unresectable, locally advanced, recurrent, or metastatic esophageal cancer has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal cancer.
  • the subject of the esophageal squamous cell carcinoma has not been previously treated for esophageal squamous cell carcinoma (e.g., lack of an effective treatment regimen).
  • the subject of the esophageal squamous cell carcinoma has not previously received radiotherapy, chemotherapy, and/or immunotherapy to treat esophageal squamous cell carcinoma.
  • the subject of the esophageal squamous cell carcinoma has not previously received systemic treatment to treat esophageal squamous cell carcinoma.
  • the subject of the esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • immune checkpoint e.g., PD-1, PD-L1, CTLA-4 or TIM-3 inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the treatment-naive esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the unresectable esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the advanced esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the locally advanced esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the recurrent and/or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the subject of the first-line esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the unresectable esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the late esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the locally advanced esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4 or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the recurrent and/or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • the subject of the unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has not previously received immune checkpoint (e.g., PD-1, PD-L1, CTLA-4, or TIM-3) inhibitors to treat esophageal squamous cell carcinoma.
  • immune checkpoint e.g., PD-1, PD-L1, CTLA-4, or TIM-3
  • the subject with esophageal cancer has previously been treated with one or more different anti-tumor therapies for esophageal cancer.
  • the subject with esophageal cancer has previously received surgery, radiation therapy, induction chemotherapy, concurrent chemotherapy, and/or adjuvant chemotherapy to treat esophageal cancer.
  • the subject with esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy to treat esophageal cancer.
  • the esophageal cancer is esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In some embodiments, the esophageal cancer is esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy. In a specific embodiment, the subject with esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy to treat esophageal cancer, and the disease relapsed 6 months (e.g., 6, 7, 8, 9, or 10 months) after stopping treatment.
  • 6 months e.g., 6, 7, 8, 9, or 10 months
  • the esophageal cancer is a locally advanced esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy. In some embodiments, the esophageal cancer is a locally advanced esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the subject of the locally advanced esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy to treat esophageal cancer, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).
  • the esophageal cancer is a recurrent and/or metastatic esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy. In some embodiments, the esophageal cancer is a recurrent and/or metastatic esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the subject of the recurrent and/or metastatic esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy to treat esophageal cancer, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).
  • the esophageal cancer is unresectable, locally advanced, recurrent or metastatic esophageal cancer that has failed neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy. In some embodiments, the esophageal cancer is unresectable, locally advanced, recurrent or metastatic esophageal cancer that has recurred after neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy.
  • the subject of the unresectable, locally advanced, recurrent or metastatic esophageal cancer has previously received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat esophageal cancer, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).
  • the subject with esophageal squamous cell carcinoma has previously been treated with one or more different anti-tumor therapies for esophageal squamous cell carcinoma.
  • the subject with esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or radical concurrent chemoradiotherapy to treat esophageal squamous cell carcinoma.
  • the esophageal squamous cell carcinoma is an esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the esophageal squamous cell carcinoma is an esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the subject of the esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).
  • the esophageal squamous cell carcinoma is a locally advanced esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the esophageal squamous cell carcinoma is a locally advanced esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the subject of the locally advanced esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).
  • the esophageal squamous cell carcinoma is a recurrent and/or metastatic esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the esophageal squamous cell carcinoma is a recurrent and/or metastatic esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy.
  • the subject of the recurrent and/or metastatic esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy, or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9, or 10 months).
  • the esophageal squamous cell carcinoma is an unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma that has failed neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy.
  • the esophageal squamous cell carcinoma is an unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma that has recurred after neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy.
  • the subject of the unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma has previously received neoadjuvant therapy, adjuvant therapy or radical synchronous chemoradiotherapy to treat esophageal squamous cell carcinoma, and the disease recurs 6 months after stopping treatment (e.g., 6, 7, 8, 9 or 10 months).
  • Embodiment 1 A drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, wherein the anti-TIM-3 antibody or the antigen-binding fragment thereof comprises:
  • HCDR1 of the amino acid sequence shown in SEQ ID NO:21 HCDR2 of the amino acid sequence shown in SEQ ID NO:22
  • HCDR3 of the amino acid sequence shown in SEQ ID NO:23 LCDR1 of the amino acid sequence shown in SEQ ID NO:24
  • LCDR2 of the amino acid sequence shown in SEQ ID NO:25 LCDR3 of the amino acid sequence shown in SEQ ID NO:26.
  • Embodiment 2 The pharmaceutical combination according to embodiment 1, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:
  • Embodiment 3 The pharmaceutical combination according to embodiment 1 or 2, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:
  • Embodiment 4 A drug combination according to any one of Embodiments 1-3, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:16.
  • Embodiment 5 A drug combination according to any one of Embodiments 1-4, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18.
  • Embodiment 6 A drug combination according to any one of Embodiments 1-5, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:19, and a light chain having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO:20.
  • Embodiment 7 A drug combination according to any one of Embodiments 1 to 6, wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for parenteral administration, preferably, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for intravenous, intramuscular or subcutaneous administration.
  • Embodiment 8 A pharmaceutical combination according to any one of Embodiments 1-7, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.
  • Embodiment 9 A pharmaceutical combination according to any one of Embodiments 1-8, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated separately.
  • Embodiment 10 A drug combination according to any one of Embodiments 1-9, wherein the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg; preferably, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 240 mg, 300 mg, 360 mg and/or 600 mg.
  • Embodiment 11 A drug combination according to any one of Embodiments 1-10, wherein the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg; preferably, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg and/or 200 mg.
  • Embodiment 12 A drug combination according to any one of Embodiments 1-11, wherein the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment to the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1.
  • Embodiment 13 A pharmaceutical combination according to any one of Embodiments 1-12, wherein the pharmaceutical combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, preferably 1200 mg or 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof; and/or
  • Embodiment 14 The drug combination according to any one of Embodiments 1-13, further comprising a chemotherapeutic drug.
  • Embodiment 15 The drug combination according to Embodiment 14, wherein the chemotherapy drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug;
  • the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin;
  • the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel.
  • Embodiment 16 The drug combination according to Embodiment 14, wherein the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.
  • Embodiment 17 A pharmaceutical combination according to any one of Embodiments 14-16, wherein the pharmaceutical combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, preferably 1200 mg or 1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof; and/or
  • Embodiment 18 The drug combination according to any one of Embodiments 14-16, wherein the drug combination is suitable for administration in a single treatment cycle, comprising 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or an antigen-binding fragment thereof, 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 , or 60-75 mg/m 2 of cisplatin, and 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 , or 135-175 mg/m 2 2 of paclitaxel; or including 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg of an anti-TIM-3 antibody or an antigen-binding fragment thereof, 10-800 mg, 50-500 mg, or 100-200 mg of an anti-PD-1 antibody or
  • Embodiment 19 Use of the pharmaceutical combination of any one of Embodiments 1-13 for the preparation of a medicament for treating a tumor in a subject.
  • Embodiment 20 The use according to Embodiment 19, wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be administered simultaneously, sequentially and/or alternately.
  • Embodiment 21 The use according to Embodiment 19 or 20, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks; optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.
  • Embodiment 22 The use according to any one of Embodiments 19-21, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.
  • Embodiment 23 Use of the drug combination of any one of Embodiments 14-18 in the preparation of a medicament for treating a tumor in a subject.
  • Embodiment 24 The use according to Embodiment 23, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately; or the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately.
  • Embodiment 25 The use according to Embodiment 23 or 24, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks; optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.
  • Embodiment 26 The use according to any one of Embodiments 23-25, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.
  • Embodiment 27 The use according to any one of Embodiments 23-26, wherein the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the cisplatin is administered once every 3 weeks; optionally, the cisplatin is administered at a dose of 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 each time, preferably, the cisplatin is administered at a dose of 60-75 mg/m 2 each time; or
  • the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the carboplatin is administered once every 3 weeks.
  • the carboplatin is administered at a dose of 2.5-5 mg/(mL/min) AUC or 3.2-5 mg/(mL/min) AUC each time.
  • the carboplatin is administered at a dose of 3.2-5 mg/(mL/min) AUC each time.
  • Embodiment 28 The use according to any one of Embodiments 23 to 27, wherein the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the paclitaxel is administered once every 3 weeks; optionally, the paclitaxel is administered at a dose of 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 each time, preferably, the paclitaxel is administered at a dose of 135-175 mg/m 2 each time.
  • Embodiment 29 The use according to any one of Embodiments 19-28, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.
  • the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.
  • Embodiment 30 The use according to Embodiment 29, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • Embodiment 31 The use according to any one of Embodiments 19-28, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
  • Embodiment 32 The use according to embodiment 31, wherein the subject with esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • Embodiment 33 A method of treating a tumor in a subject, wherein the method comprises administering to the subject the drug combination of any one of Embodiments 1-18.
  • Embodiment 34 A method according to embodiment 33, wherein the method comprises administering to the subject the drug combination of any one of embodiments 14-18 in a first treatment phase, and administering to the subject the drug combination of any one of embodiments 1-13 in a second treatment phase.
  • Embodiment 35 The method according to embodiment 33 or 34, wherein the first treatment phase comprises 1-14 treatment cycles, 2-12 treatment cycles or 2-10 treatment cycles, preferably 2-8 treatment cycles, and more preferably 4-6 treatment cycles.
  • Embodiment 36 The method according to embodiment 35, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, one treatment cycle is every 3 weeks.
  • Embodiment 37 A method according to any one of Embodiments 33-36, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without indication for local radical treatment.
  • the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without indication for local radical treatment.
  • Embodiment 38 The use according to Embodiment 37, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • Embodiment 39 The use according to any one of Embodiments 33-36, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
  • Embodiment 40 The use according to Embodiment 39, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • Embodiment 41 A kit for treating a tumor, comprising the pharmaceutical combination according to any one of Embodiments 1-18.
  • a combination drug comprising:
  • Embodiment 43 The combination drug combination according to Embodiment 42, wherein the first treatment phase comprises 1-14 treatment cycles, 2-12 treatment cycles or 2-10 treatment cycles, preferably 2-8 treatment cycles, and more preferably 4-6 treatment cycles.
  • Embodiment 44 The combination drug combination according to Embodiment 43, wherein one treatment cycle is every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, one treatment cycle is every 3 weeks.
  • Embodiment 45 Use of the combination drug combination described in any one of Embodiments 42-44 in the preparation of a medicament for treating a tumor in a subject.
  • Embodiment 46 The use according to Embodiment 45, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma with no indication for local radical treatment.
  • Embodiment 47 The use according to Embodiment 46, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • Embodiment 48 The use according to Embodiment 45, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
  • Embodiment 49 The use according to Embodiment 48, wherein the subject suffering from esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • Embodiment 50 Use of an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof in the preparation of a medicament for treating a tumor in a subject, wherein the anti-TIM-3 antibody or the antigen-binding fragment thereof comprises:
  • HCDR1 of the amino acid sequence shown in SEQ ID NO:21 HCDR2 of the amino acid sequence shown in SEQ ID NO:22
  • HCDR3 of the amino acid sequence shown in SEQ ID NO:23 LCDR1 of the amino acid sequence shown in SEQ ID NO:24
  • LCDR2 of the amino acid sequence shown in SEQ ID NO:25 LCDR3 of the amino acid sequence shown in SEQ ID NO:26.
  • Embodiment 51 Use of an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, and a chemotherapeutic drug in the preparation of a medicament for treating a tumor in a subject, wherein the anti-TIM-3 antibody or an antigen-binding fragment thereof comprises:
  • HCDR1 of the amino acid sequence shown in SEQ ID NO:21 HCDR2 of the amino acid sequence shown in SEQ ID NO:22
  • HCDR3 of the amino acid sequence shown in SEQ ID NO:23 LCDR1 of the amino acid sequence shown in SEQ ID NO:24
  • LCDR2 of the amino acid sequence shown in SEQ ID NO:25 LCDR3 of the amino acid sequence shown in SEQ ID NO:26;
  • the chemotherapy drug is a platinum anti-tumor drug and/or a taxane anti-tumor drug
  • the platinum anti-tumor drug is selected from one or more of cisplatin, carboplatin, nedaplatin, dicycloplatin, picoplatin, oxaliplatin, miplatin, lobaplatin, levoplatin, triplatin tetranitrate, phenoplatin and satraplatin;
  • the taxane anti-tumor drug is selected from one or more of paclitaxel, cabazitaxel and docetaxel;
  • the chemotherapy drugs are cisplatin and paclitaxel, or the chemotherapy drugs are carboplatin and paclitaxel.
  • Embodiment 52 The use according to embodiment 50 or 51, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:
  • Embodiment 53 The use according to any one of Embodiments 50-52, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof comprises:
  • Embodiment 54 The use according to any one of Embodiments 50-53, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: HCDR1 of the amino acid sequence shown in SEQ ID NO:11, HCDR2 of the amino acid sequence shown in SEQ ID NO:12, HCDR3 of the amino acid sequence shown in SEQ ID NO:13, LCDR1 of the amino acid sequence shown in SEQ ID NO:14, LCDR2 of the amino acid sequence shown in SEQ ID NO:15, and LCDR3 of the amino acid sequence shown in SEQ ID NO:16.
  • Embodiment 55 The use according to any one of Embodiments 50-54, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises: a heavy chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 17, and a light chain variable region having an amino acid sequence that is at least 95% identical to the amino acid sequence shown in SEQ ID NO: 18.
  • Embodiment 56 The use according to any one of Embodiments 50-55, wherein the anti-PD-1 antibody or antigen-binding fragment thereof
  • the invention comprises: a heavy chain having an amino acid sequence at least 95% identical to the amino acid sequence shown in SEQ ID NO: 19, and a light chain having an amino acid sequence at least 95% identical to the amino acid sequence shown in SEQ ID NO: 20.
  • Embodiment 57 The use according to any one of Embodiments 50-56, wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for parenteral administration, preferably, the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment are formulated as a preparation for intravenous, intramuscular or subcutaneous administration.
  • Embodiment 58 The use according to any one of Embodiments 50-57, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated in a single formulation.
  • Embodiment 59 The use according to any one of Embodiments 50-58, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof and the anti-PD-1 antibody or antigen-binding fragment thereof are formulated separately.
  • Embodiment 60 The use according to any one of Embodiments 50-59, wherein the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 60-1800 mg, 100-1600 mg, 120-1600 mg, 180-1200 mg, or 240-600 mg; preferably, the unit dose of the anti-TIM-3 antibody or its antigen-binding fragment is 240 mg, 300 mg, 360 mg and/or 600 mg.
  • Embodiment 61 The use according to any one of Embodiments 50-60, wherein the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 10-500 mg, 50-500 mg, 50-200 mg, or 100-200 mg; preferably, the unit dose of the anti-PD-1 antibody or its antigen-binding fragment is 100 mg and/or 200 mg.
  • Embodiment 62 The use according to any one of Embodiments 50-61, wherein the mass ratio of the anti-TIM-3 antibody or its antigen-binding fragment to the anti-PD-1 antibody or its antigen-binding fragment is (0.1-180):1, (0.2-50):1, (0.5-9):1, (3-7.5):1, (4-7.5):1 or (6-7.5):1.
  • Embodiment 63 The use according to any one of Embodiments 50-62, wherein the anti-TIM-3 antibody or its antigen-binding fragment and the anti-PD-1 antibody or its antigen-binding fragment can be administered simultaneously, sequentially and/or alternately.
  • Embodiment 64 The use according to any one of Embodiments 50-62, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, cisplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately; or the anti-TIM-3 antibody or antigen-binding fragment thereof, anti-PD-1 antibody or antigen-binding fragment thereof, carboplatin and paclitaxel can be administered simultaneously, sequentially and/or alternately.
  • Embodiment 65 The use according to any one of Embodiments 50-64, wherein the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered once every 3 weeks; optionally, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 100-1800 mg, 600-1800 mg, 600-1500 mg, or 1200-1500 mg each time, preferably, the anti-TIM-3 antibody or antigen-binding fragment thereof is administered at a dose of 1200 mg each time.
  • Embodiment 66 The use according to any one of Embodiments 50-65, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks. Preferably, the anti-PD-1 antibody or antigen-binding fragment thereof is administered once every 3 weeks.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 10-800 mg, 50-500 mg, or 100-200 mg each time.
  • the anti-PD-1 antibody or antigen-binding fragment thereof is administered at a dose of 200 mg each time.
  • Embodiment 67 The use according to any one of Embodiments 50-66, wherein the cisplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the cisplatin is administered once every 3 weeks; optionally, the cisplatin is administered at a dose of 30-100 mg/m 2 , 30-75 mg/m 2 , 48-75 mg/m 2 or 60-75 mg/m 2 each time, preferably, the cisplatin is administered at a dose of 60-75 mg/m 2 each time; or the carboplatin is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the carboplatin is administered once every 3 weeks; optionally, the carboplatin is administered at a dose of 2.5-5 mg/(mL/min)AUC or 3.2-5 mg/(mL/min)AUC each time, preferably, the carboplatin is administered at a dose of 3.2-5 mg/(mL/min)AUC
  • Embodiment 68 The use according to any one of Embodiments 50 to 67, wherein the paclitaxel is administered once every 1 week, every 2 weeks, every 3 weeks, or every 4 weeks, preferably, the paclitaxel is administered once every 3 weeks; optionally, the paclitaxel is administered at a dose of 75-175 mg/m 2 , 100-175 mg/m 2 , 112-175 mg/m 2 or 135-175 mg/m 2 each time, preferably, the paclitaxel is administered at a dose of 135-175 mg/m 2 each time.
  • Embodiment 69 The use according to any one of Embodiments 50-68, wherein the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications.
  • the tumor is head and neck cancer; preferably, the tumor is head and neck squamous cell carcinoma; preferably, the tumor is locally advanced, recurrent or metastatic head and neck squamous cell carcinoma without local radical treatment indications.
  • Embodiment 70 The use according to Embodiment 69, wherein the subject with head and neck squamous cell carcinoma has not previously received systemic treatment for head and neck squamous cell carcinoma.
  • Embodiment 71 The use according to any one of Embodiments 50-68, wherein the tumor is esophageal cancer; preferably, the tumor is esophageal squamous cell carcinoma; preferably, the tumor is unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
  • Embodiment 72 The use according to Embodiment 71, wherein the subject with esophageal squamous cell carcinoma has not previously received systemic treatment for esophageal squamous cell carcinoma.
  • the combination has good anti-tumor activity and exhibits a more excellent anti-tumor synergistic effect.
  • the drug combination and treatment regimen disclosed herein have good efficacy in treating head and neck cancer, especially recurrent or metastatic head and neck squamous cell carcinoma, and have beneficial effects on at least one of ORR, DCR, DOR, PFS, 9-month PFS rate, 6-month PFS rate, OS, tolerability and side effects, for example, improving the 9-month PFS rate and/or 6-month PFS rate of patients.
  • the drug combination and treatment regimen disclosed herein have good efficacy in treating esophageal cancer, especially unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma, and have beneficial effects on at least one of ORR, DCR, DOR, PFS, 9-month PFS rate, 6-month PFS rate, OS, tolerance and side effects, for example, improving the patient's ORR, PFS, 9-month PFS rate and/or 6-month PFS rate.
  • drug combination refers to a combination of two or more active ingredients (including administration in the form of each active ingredient itself, or in the form of its respective pharmaceutically acceptable salt or ester derivatives, prodrugs or compositions) administered simultaneously or sequentially.
  • the active ingredients can be administered to the subject simultaneously as a single formulation, or each as a single formulation in any order.
  • all of the active ingredients are formulated in a single formulation and administered to the subject simultaneously.
  • part of the active ingredients are formulated in a single formulation and the other parts of the active ingredients are each administered to the subject simultaneously or sequentially in any order as a single formulation.
  • fixed combination means that the active ingredients are administered to a subject simultaneously in a fixed total dose or dose ratio, or in the form of a single entity, pharmaceutical composition or formulation.
  • non-fixed combination refers to two or more active ingredients administered to a subject as independent entities (e.g., pharmaceutical compositions, preparations) simultaneously, concurrently or sequentially, wherein the active ingredients administered to the subject reach a therapeutically effective level.
  • An example of a non-fixed combination is cocktail therapy, such as the administration of three or more active ingredients.
  • the individual active ingredients may be packaged, sold or administered as completely independent pharmaceutical compositions.
  • the "non-fixed combination” also includes the combined use of "fixed combinations” or "fixed combinations” with any one or more independent entities of the active ingredients.
  • the term "antibody” refers to an antigen binding protein having at least one antigen binding domain.
  • the antibodies and fragments thereof disclosed herein may be whole antibodies or any fragments thereof. Therefore, the antibodies and fragments thereof disclosed herein include monoclonal antibodies or fragments thereof and antibody variants or fragments thereof. Examples of antibody and antigen binding fragment fragments thereof include monospecific antibodies, bispecific antibodies, multispecific antibodies, Fab fragments, Fab' fragments, F(ab)' 2 fragments, Fv fragments, isolated CDR regions, single-chain Fv molecules (scFv) and other antibody fragments known in the art.
  • the anti-TIM-3 antibodies and anti-PD-1 antibodies and antigen binding fragments thereof disclosed herein may be IgG1, IgG2, IgG3 or IgG4 isotypes.
  • the term "isotype" refers to the antibody species encoded by the heavy chain constant region gene.
  • the anti-TIM-3 antibodies and antigen binding fragments thereof disclosed herein and anti-PD-1 antibodies and antigen binding fragments thereof may be derived from any species, including but not limited to mice, rats, rabbits, primates, llamas and humans.
  • the anti-TIM-3 antibodies and antigen-binding fragments thereof and anti-PD-1 antibodies and antigen-binding fragments thereof of the present disclosure may be murine antibodies, chimeric antibodies, humanized antibodies or fully human antibodies.
  • the “antibody” of the present disclosure includes the whole antibody and any antigen-binding fragment thereof (or “antibody”).
  • the conventional "whole antibody” is a glycoprotein comprising two heavy (H) chains and two light (L) chains, which are connected by disulfide bonds.
  • Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH).
  • the heavy chain constant region consists of three domains, namely CH1, CH2 and CH3.
  • Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL).
  • the light chain constant region consists of one domain CL.
  • the VH and VL regions can also be divided into hypervariable regions, namely complementarity determining regions (CDRs), and framework regions (FRs) with relatively conservative sequences.
  • CDRs complementarity determining regions
  • FRs framework regions
  • Each VH and VL is respectively It is composed of three CDRs and four FRs, which are respectively: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from the amino terminus to the carboxyl terminus.
  • the variable regions of the heavy and light chains contain binding domains that interact with antigens.
  • the constant region of the antibody can mediate the binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system.
  • special "whole antibodies" such as nanobodies, have only heavy (H) chains and no light (L) chains.
  • an "antigen-binding fragment” or “antibody binding portion” of an antibody refers to one or more fragments of an antibody that retain the function of specifically binding to an antigen (e.g., TIM-3 or PD-1). It has been demonstrated that the antigen-binding function of an antibody can be implemented by a fragment of the entire antibody.
  • Examples encompassed within the term "antigen-binding portion/fragment" of an antibody include: (i) Fab fragment: a monovalent fragment consisting of VL , VH , CL, and CH1 domains; (ii) F(ab')2 fragment, a bivalent fragment comprising two Fab fragments disulfide-bridged at the hinge region; (iii) Fd fragment consisting of VH and CH1 domains; (iv) Fv fragment consisting of the VL and VH domains of a single antibody arm; (v) dAb fragment consisting of a VH domain (see Ward et al., Nature.
  • VH and VL can be connected into a single protein chain by a recombinant method through a synthetic linker, wherein VL and VH are paired to form a monovalent molecule (called single-chain Fv (scFv); see, for example, Bird et al., Science. 242: 423-426 (1988); Huston et al., Proc. Natl. Acad. Sci. 85: 5879-5883 (1988)).
  • scFv single-chain Fv
  • antigen binding portion/fragment single-chain antibodies are also encompassed in the term antigen binding portion/fragment.
  • recombinant polypeptides, fusion proteins and immunoconjugates comprising the antigen binding portion/fragment are also encompassed in the term antigen binding portion/fragment.
  • a “chimeric antibody” is an antibody having at least a portion of a heavy chain variable region and at least a portion of a light chain variable region derived from one species; and at least a portion of a constant region derived from another species.
  • a chimeric antibody may comprise a murine variable region and a human constant region.
  • Humanized antibodies are antibodies that contain complementary determining regions (CDRs) derived from non-human antibodies, and framework regions and constant regions derived from human antibodies.
  • CDRs complementary determining regions
  • anti-TIM-3 antibodies and anti-PD-1 antibodies may contain CDRs derived from one or more murine antibodies, as well as human framework regions and human constant regions.
  • Exemplary humanized antibodies are provided herein. Additional anti-TIM-3 antibodies or variants thereof comprising HCDRs and LCDRs provided herein may be produced using any human framework sequence, and are also included in the present disclosure. Additional anti-PD-1 antibodies or variants thereof comprising HCDRs and LCDRs provided herein may be produced using any human framework sequence, and are also included in the present disclosure.
  • framework sequences suitable for use in the present disclosure include those framework sequences that are structurally similar to the framework sequences provided herein. Additional modifications may be made in the framework region to improve the properties of the antibodies provided herein. Such additional framework modifications may include chemical modifications; point mutations to reduce immunogenicity or remove T cell epitopes; or mutations may be returned to residues in the original germline sequence. In some embodiments, such modifications include those corresponding to the mutations exemplified herein, including back mutations to the germline sequence. For example, in one embodiment, one or more amino acids in the human framework regions of the VH and/or VL of the humanized antibodies provided herein are backmutated to the corresponding amino acids in the parent murine antibody.
  • identity is also known as consistency.
  • the "percentage (%) identity” of an amino acid sequence refers to the percentage of amino acid residues in the sequence to be compared that are identical to the amino acid residues in the specific amino acid sequence shown in this article, after comparing the sequence to be compared with the specific amino acid sequence shown in this article and introducing spaces if necessary to achieve the maximum sequence identity percentage, and not considering any conservative substitutions as part of the sequence identity.
  • the amino acid sequence alignment of identity can be carried out in a variety of ways within the scope of the art, such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine the appropriate parameters for comparing sequences, including any algorithm required to obtain the maximum alignment in the full length of the comparison sequence.
  • treatment generally refers to an operation to obtain a desired pharmacological and/or physiological effect.
  • the effect may be preventive, in terms of completely or partially preventing a disease or its symptoms; and/or therapeutic, in terms of partially or completely stabilizing or curing a disease and/or side effects produced by the disease.
  • treatment encompasses any treatment of a patient's disease, including but not limited to preventing the occurrence or recurrence of a disease, alleviating symptoms of a disease, reducing any direct or indirect pathological consequences of a disease, preventing the metastasis of a disease, slowing the progression of a disease, improving or alleviating the state of a disease, extending the frequency and duration of symptom-free periods, and resolving or improving the prognosis of a disease.
  • a “therapeutically effective amount” or “therapeutically effective dose” is an amount that, when used alone or in combination with one or more other therapeutic agents, protects a subject from Any amount of a drug that inhibits the onset of disease or promotes disease regression, as evidenced by a reduction in the severity of disease symptoms, an increase in the frequency and duration of disease symptom-free periods, or the prevention of impairment or disability resulting from disease affliction.
  • the ability of a therapeutic agent to promote disease regression can be evaluated using a variety of methods known to skilled practitioners, such as in human subjects during clinical trials, in animal model systems predictive of efficacy in humans, or by measuring the activity of the agent in in vitro assays.
  • a “treatment phase” refers to a period of time during which a drug combination (e.g., a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof and an anti-PD-1 antibody or an antigen-binding fragment thereof, or a drug combination comprising an anti-TIM-3 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof and a chemotherapeutic drug (e.g., cisplatin and paclitaxel, or carboplatin and paclitaxel)) is administered to a subject.
  • the "first treatment phase” is the initial treatment phase, which may be an induction treatment phase
  • the “second treatment phase” is the treatment phase after the first treatment phase ends, which may be a maintenance treatment phase.
  • administering refers to the physical introduction of a therapeutic agent into a subject using any of a variety of methods and delivery systems known to those skilled in the art.
  • the administration route of the antibody or its antigen-binding fragment includes intravenous, intramuscular, subcutaneous, intraperitoneal, spinal or other parenteral administration routes, such as by injection or infusion.
  • parenteral administration refers to a mode of administration other than enteral administration, which is usually performed by injection, and includes, but is not limited to, intravenous, intramuscular, intraarterial, intrathecal, intralymphatic, intralesional, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcutaneous, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion, and in vivo electroporation. Administration can also be performed, for example, once, multiple times, and/or in one or more extended time periods.
  • flat dose is used to refer to the dose administered to a patient regardless of the patient's weight or body surface area (BSA).
  • the flat dose is therefore specified as an absolute amount of an agent (e.g., an anti-TIM-3 antibody or antigen-binding fragment thereof) rather than as a mg/kg dose.
  • an agent e.g., an anti-TIM-3 antibody or antigen-binding fragment thereof
  • mg/kg dose e.g., a 60 kg person and a 100 kg person will receive the same dose of antibody (e.g., 1200 mg of an anti-TIM-3 antibody or antigen-binding fragment thereof).
  • pharmaceutically acceptable refers to those compounds, materials, compositions and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response or other problems or complications, commensurate with a reasonable benefit/risk ratio.
  • pharmaceutical composition refers to a mixture of one or more active ingredients of the present disclosure or a pharmaceutical combination thereof and a pharmaceutically acceptable carrier.
  • the purpose of a pharmaceutical composition is to facilitate administration of a compound of the present disclosure or a pharmaceutical combination thereof to a subject.
  • pharmaceutical composition and “preparation” have the same meaning and are used interchangeably.
  • the terms “subject,” “patient,” or “subject” are used interchangeably.
  • “Subject,” “patient,” or “subject” includes any human or non-human animal.
  • the term “non-human animal” includes, but is not limited to, vertebrates such as non-human primates, sheep, dogs, and rodents such as mice, rats, and guinea pigs.
  • the terms “subject,” “patient,” or “subject” are mammals.
  • the subject, patient, or subject is a mouse.
  • the subject, patient, or subject is a human.
  • “combination” or “combined use” means that two or more active substances can be administered to a subject simultaneously as a single formulation, or sequentially in any order as a single formulation.
  • all of the active ingredients are formulated in a single formulation and administered to a subject simultaneously.
  • part of the active ingredients are formulated in a single formulation and the other parts of the active ingredients are each administered to a subject simultaneously or sequentially in any order as a single formulation.
  • single dose refers to the smallest packaging unit containing a certain amount of medicine, for example, if a box of medicine contains seven tablets, then one tablet is a single dose; or a bottle of injection is a single dose.
  • multiple doses consists of multiple single doses.
  • Unit dose refers to the dose of active ingredient contained in the smallest packaging unit containing a certain amount of medicine, for example, the dose of antibody contained in a bottle of antibody injection is a unit dose.
  • recurrent cancer is a cancer that regenerates in the original site or at a distant site after responding to initial treatment (eg, surgery).
  • a "locally recurrent” cancer is a cancer that recurs after treatment in the same location as a previously treated cancer.
  • metalastatic cancer refers to cancer that has spread from one part of the body (such as the mouth) to another part of the body.
  • refractory refers to a condition in which a subject or mammal has residual cancer cells in its body even after intensive treatment.
  • treatment failure is defined as disease progression or recurrence during treatment or after the last treatment, or intolerable toxic side effects during treatment.
  • first-line treatment refers to the drug that can be selected first or standardly based on the patient's condition.
  • “about” means within the acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” may mean within 1 or more than 1 standard deviation as practiced in the art. Alternatively, “about” may mean a range of up to ⁇ 5%, such as fluctuations within ⁇ 2%, within ⁇ 1%, or within ⁇ 0.5% of a given specific numerical range. When a specific value is given in the present disclosure or claims, unless otherwise indicated, the meaning of "about” should be considered to be within the acceptable error range for that specific value. In this document, unless otherwise indicated, all values of drug doses, times, step parameters, or conditions are modified by "about” by default.
  • the entire contents of the CN106977602A patent application document are incorporated herein.
  • the heavy chain amino acid sequence of the anti-PD-1 antibody in the following embodiments is shown in SEQ ID NO: 19 of the present disclosure, and the light chain amino acid sequence is shown in SEQ ID NO: 20 of the present disclosure.
  • Example 1 Clinical trial of head and neck squamous cell carcinoma
  • R/M HNSCC recurrent or metastatic head and neck squamous cell carcinoma
  • TBIL Serum total bilirubin
  • UPN upper limit of normal
  • ALT Alanine aminotransferase
  • AST aspartate aminotransferase
  • LVEF left ventricular ejection fraction
  • Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the end of the study; the serum pregnancy test should be negative within 7 days before study entry, and the subjects must be non-breastfeeding; male subjects should agree to use contraceptive measures during the study and within 6 months after the end of the study.
  • contraceptive measures such as intrauterine devices, birth control pills or condoms
  • Anti-PD-1 antibody injection (Specification: 100 mg/10 mL/bottle, provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): 3 weeks is one treatment cycle (dosing time window: ⁇ 3 days), administered by intravenous infusion, with a dose of 200 mg of anti-PD-1 antibody administered once on the first day of each treatment cycle.
  • Anti-TIM-3 antibody injection (specification: 240 mg/4 mL/bottle, or 600 mg/10 mL/bottle, provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): 3 weeks is a treatment cycle (dosing time window: ⁇ 3 days), administered by intravenous infusion, with a dose of 1200 mg of anti-TIM-3 antibody administered once on the first day of each treatment cycle.
  • Paclitaxel (provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): One treatment cycle is 3 weeks, and 175 mg/ m2 of paclitaxel is administered once on the first day of each treatment cycle through intravenous infusion.
  • Cisplatin provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
  • One treatment cycle is 3 weeks, and it is administered once on the first day of each treatment cycle at a dose of 75 mg/ m2 of cisplatin via intravenous infusion.
  • the dosage of carboplatin needs to be calculated based on the area under the plasma concentration-time curve (AUC) and endogenous creatinine clearance.
  • AUC area under the plasma concentration-time curve
  • Carboplatin dosage (mg) set AUC (mg/(mL/min)) ⁇ [creatinine clearance (mL/min) + 25]
  • Creatinine clearance was calculated using the Cockcroft-Gault formula:
  • the first treatment phase (initial treatment phase): anti-TIM-3 antibody injection + anti-PD-1 antibody injection + paclitaxel + cisplatin, or anti-TIM-3 antibody injection + anti-PD-1 antibody injection + paclitaxel + carboplatin; 4-6 treatment cycles.
  • the order of administration is: anti-PD-1 antibody injection ⁇ anti-TIM-3 antibody injection ⁇ paclitaxel ⁇ cisplatin or carboplatin.
  • the second treatment phase (maintenance treatment phase): anti-TIM-3 antibody injection + anti-PD-1 antibody injection, treatment until disease progression or intolerable toxicity.
  • Order of administration anti-PD-1 antibody injection ⁇ anti-TIM-3 antibody injection.
  • the second treatment phase follows the first treatment phase.
  • PD-1 antibody injection Delayed medication is allowed, but the longest delay should not exceed 12 weeks.
  • Anti-TIM-3 antibody injection Delayed medication is allowed, but the longest delay should not exceed 12 weeks.
  • the efficacy evaluation criteria were based on RECIST 1.1, and the iRECIST criteria were used to confirm the efficacy.
  • the NCI-CTC AE 5.0 criteria were used to judge the severity of adverse events.
  • ORR Objective response rate
  • PFS progression-free survival
  • OS overall survival
  • CBR clinical benefit rate
  • DOR duration of response
  • Adverse event rate the incidence and severity of all adverse events (AEs) and serious adverse events (SAEs), as well as abnormal laboratory test indicators.
  • anti-TIM-3 antibody injection + anti-PD-1 antibody injection + paclitaxel + cisplatin After 6 cycles of anti-TIM-3 antibody injection + anti-PD-1 antibody injection + paclitaxel + cisplatin, anti-TIM-3 antibody injection + anti-PD-1 antibody injection were used for maintenance treatment.
  • the target lesion size and evaluation results are as follows:
  • target lesion 54.91 mm
  • target lesion 43.01 mm
  • target lesion 13.47 mm
  • Treatment was given for 6 cycles, target lesion: 5 mm;
  • Treatment was given for 8 cycles, target lesion: 5 mm;
  • the best efficacy of the patient was PR.
  • target lesion 34.25 mm
  • target lesion 26.33 mm
  • target lesion 20.36 mm
  • the best efficacy of the patient was PR.
  • target lesion 30.06 mm
  • target lesion 17.4 mm
  • target lesion 10.94 mm
  • Treatment was given for 6 cycles, target lesion: 10.3 mm;
  • the best efficacy of the patient was PR.
  • target lesion 38.52 mm
  • target lesion 25.07 mm
  • target lesion 15.9 mm
  • target lesion 9.4 mm
  • the best efficacy of the patient was PR.
  • target lesion 37.4 mm
  • Treatment was given for 2 cycles, target lesion: 20 mm;
  • target lesion 16.8 mm
  • Treatment was given for 6 cycles, target lesion: 16.6 mm;
  • the best efficacy of the patient was PR.
  • target lesion 22.4 mm
  • target lesion 18.8 mm
  • target lesion 12.7 mm
  • the best efficacy of the patient was PR.
  • Example 2 Clinical trial of esophageal squamous cell carcinoma
  • ANC Neutrophil count
  • TBIL Serum total bilirubin
  • ALT Alanine aminotransferase
  • AST aspartate aminotransferase
  • Thyroid stimulating hormone (TSH) ⁇ ULN Thyroid stimulating hormone (TSH) ⁇ ULN; if abnormal, T3 and T4 levels should be examined; if T3 and T4 levels are normal, the patient can be selected.
  • TSH thyroid stimulating hormone
  • LVEF left ventricular ejection fraction
  • Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, birth control pills or condoms) during the study and within 6 months after the end of the study; the serum pregnancy test should be negative within 7 days before study entry, and the subjects must be non-breastfeeding; male subjects should agree to use contraceptive measures during the study and within 6 months after the end of the study.
  • contraceptive measures such as intrauterine devices, birth control pills or condoms
  • Anti-PD-1 antibody injection (Specification: 100 mg/10 mL/bottle, provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): 3 weeks is one treatment cycle (dosing time window: ⁇ 3 days), administered by intravenous infusion, with a dose of 200 mg of anti-PD-1 antibody administered once on the first day of each treatment cycle.
  • Anti-TIM-3 antibody injection (specification: 240 mg/4 mL/bottle, or 600 mg/10 mL/bottle, provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): 3 weeks is a treatment cycle (dosing time window: ⁇ 3 days), administered by intravenous infusion, with a dose of 1200 mg of anti-TIM-3 antibody administered once on the first day of each treatment cycle.
  • Paclitaxel (provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.): One treatment cycle is 3 weeks, and paclitaxel is administered once on the first day of each treatment cycle via intravenous infusion at a dose of 135-150 mg/ m2 .
  • Cisplatin provided by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
  • One treatment cycle is 3 weeks, and it is administered once on the first day of each treatment cycle by intravenous infusion at a dose of 60-75 mg/ m2 of cisplatin.
  • the first treatment phase (initial treatment phase): anti-TIM-3 antibody injection + anti-PD-1 antibody injection + paclitaxel + cisplatin; 4-6 treatment cycles.
  • Order of administration PD-1 antibody injection first, then anti-TIM-3 antibody injection, cisplatin after paclitaxel.
  • the second treatment phase (maintenance treatment phase): anti-TIM-3 antibody injection + anti-PD-1 antibody injection, treatment until disease progression or intolerable toxicity.
  • Order of administration anti-PD-1 antibody injection ⁇ anti-TIM-3 antibody injection.
  • the second treatment phase follows the first treatment phase.
  • PD-1 antibody injection Delayed medication is allowed, but the longest delay should not exceed 12 weeks.
  • Anti-TIM-3 antibody injection Delayed medication is allowed, but the longest delay should not exceed 12 weeks.
  • the efficacy evaluation criteria were based on RECIST 1.1, and the iRECIST criteria were used to confirm the efficacy.
  • the NCI-CTC AE 5.0 criteria were used to judge the severity of adverse events.
  • ORR Objective response rate
  • PFS progression-free survival
  • OS overall survival
  • DOR duration of response
  • Adverse event rate the incidence and severity of all adverse events (AEs) and serious adverse events (SAEs), as well as abnormal laboratory test indicators.
  • lymph node target lesions 15.2 mm;
  • lymph node target lesion 8 mm
  • lymph node target lesions 8 mm
  • lymph node target lesions 8.8 mm
  • lymph node target lesions 8.5 mm;
  • the best efficacy of the patient was CR.
  • lymph node target lesions 30 mm;
  • lymph node target lesions 17 mm;
  • lymph node target lesions 16 mm;
  • lymph node target lesions 16 mm
  • the target lesion of lymph nodes was 16 mm.
  • the best efficacy of the patient was PR.
  • target lesion 76.71 mm
  • the target lesion of lymph nodes was 41.16 mm;
  • the target lesion of lymph nodes was 29.08 mm;
  • the best efficacy of the patient was PR.
  • lymph node target lesions 137.3 mm;
  • lymph node target lesions 79.7 mm
  • lymph node target lesions 62.3 mm
  • the best efficacy of the patient was PR.

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Abstract

提供含抗TIM-3抗体的药物组合，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；任选地，还包括化疗药物。还提供用于治疗肿瘤的试剂盒，其包含所述药物组合。此外，还提供所述药物组合在制备用于治疗肿瘤的药物中的用途以及所述药物组合治疗肿瘤的方法。

Description

含抗TIM-3抗体的药物组合
本公开要求如下所示的优先权，其全部内容通过引用结合在本公开中：
CN202310201537.3，申请日2023年03月03日；
CN202310407301.5，申请日2023年04月14日；
CN202310399024.8，申请日2023年04月14日。
技术领域
本公开属于生物医药领域，具体涉及结合TIM-3的抗体与结合PD-1的抗体的药物组合。
背景技术
T细胞免疫球蛋白和粘蛋白结构域蛋白3(T cell immunoglobulin and mucin domain-containing protein 3，TIM-3)，也称为甲型肝炎病毒细胞受体2(Hepatitis A Virus Cellular Receptor 2，HAVCR2)，是免疫调节蛋白TIM家族成员(人TIM家族包括TIM-1、3、4)，TIM-3选择性地表达于活化的Th1细胞表面，还在髓细胞、DC细胞、NK细胞、巨噬细胞上表达，同时也在多种肿瘤细胞上表达。TIM-3具有多种不同的配体，包括半乳凝素9(Galectin9)、磷酯酰丝氨酸(PtdSer)、高迁移族蛋白B1(HMGB1)和癌胚抗原细胞黏附分子1(CEACAM1)。TIM-3作为一种免疫检查点，其生理功能为负向调节机体的免疫作用，避免过强的免疫作用或自身免疫作用对机体的损伤。越来越多的证据表明，TIM-3蛋白和/或mRNA在多种肿瘤组织和肿瘤相关的免疫细胞上表达上调，参与肿瘤免疫逃逸和免疫应答，促进肿瘤的发展。
PD-1(Programmed death-1，程序性死亡受体1)是一种由活化的T淋巴细胞和B淋巴细胞表达的关键免疫检查点受体并介导免疫抑制，其配体包括PD-L1和PD-L2。中国专利文献CN106977602A公开了一种抗PD-1单克隆抗体14C12H1L1，该单克隆抗体能够有效地阻断PD-1与PD-L1的结合，显示出较好的抗肿瘤活性。
头颈癌是一组广泛发生于鼻窦、鼻腔、口腔及咽喉等部位上皮细胞的恶性肿瘤，其中超过90％为头颈部鳞状细胞癌(HNSCC)。我国头颈部肿瘤的死亡比例远高于其他国家，约70％-80％的患者在初诊时已为局部晚期(即Ⅲ或Ⅳ期)，局晚期经根治性治疗后，约55％的患者会发生复发或转移。因此，迫切需要探索出能够治疗头颈癌患者的其他药物，提高治疗效果。
食管癌是常见的消化系统恶性肿瘤之一，90％以上的食管癌为鳞状细胞癌。尽管通过标准治疗方案可以提高患者的临床获益，但仍有大多数患者会出现获得性耐药。因此，迫切需要探索出能够治疗食管癌患者的其他药物，提高治疗效果。
发明概述
在一方面，本公开提供一种药物组合，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；任选地，还包括化疗药物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述药物组合包括单位剂量为60-1800mg的抗TIM-3抗体或其抗原结合片段和单位剂量为10-500mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括单位剂量为60-1800mg的抗TIM-3抗体或其抗原结合片段、单位剂量为10-500mg的抗PD-1抗体或其抗原结合片段和化疗药物。在一些实施方案中，所述药物组合包括单位剂量为60-1800mg的抗TIM-3抗体或其抗原结合片段、单位剂量为10-500mg的抗PD-1抗体或其抗原结合片段、单位剂量为2.5-100mg的顺铂和单位剂量为30-150mg的紫杉醇。在一些实施方案中，所述药物组合包括单位剂量为60-1800mg的抗TIM-3抗体或其抗原结合片段、单位剂量为10-500mg的抗PD-1抗体或其抗原结合片段、单位剂量为50-450mg的卡铂和单位剂量为30-150mg的紫杉醇。
在一些实施方案中，所述药物组合包括100-1800mg的抗TIM-3抗体或其抗原结合片段和10-800mg 的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段和化疗药物。在一些实施方案中，所述药物组合包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段、30-100mg/m2的顺铂、和75-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段、2.5-5mg/(mL/min)AUC的卡铂、和75-175mg/m2的紫杉醇。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg的抗TIM-3抗体或其抗原结合片段和10-800mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段和化疗药物。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段、30-100mg/m2的顺铂、和75-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg的抗TIM-3抗体或其抗原结合片段、10-800mg的抗PD-1抗体或其抗原结合片段、2.5-5mg/(mL/min)AUC的卡铂和75-175mg/m2的紫杉醇。
在一些实施方案中，所述药物组合用于治疗肿瘤。
在另一方面，本公开还提供在受试者中治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的药物组合。本公开还提供在受试者中一线治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的药物组合。本公开还提供在受试者中治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予治疗有效量的本公开的药物组合，并且在第二治疗阶段向受试者给予治疗有效量的本公开的药物组合。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予治疗有效量的本公开的药物组合，并且在第二治疗阶段向受试者给予治疗有效量的本公开的药物组合。
另一方面，本公开还提供了本公开的药物组合在制备用于治疗受试者中肿瘤的药物中的用途。本公开还提供了本公开的药物组合在制备用于一线治疗受试者中肿瘤的药物中的用途。另外，本公开还提供了本公开的药物组合治疗受试者中肿瘤的用途。本公开还提供了本公开的药物组合一线治疗受试者中肿瘤的用途。在一些实施方案中，所述用途包括向受试者给予治疗有效量的本公开的药物组合。在一些实施方案中，所述用途包括在第一治疗阶段向受试者给予治疗有效量的本公开的药物组合，并且在第二治疗阶段向受试者给予治疗有效量的本公开的药物组合。
另一方面，本公开还提供治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。本公开还提供治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。本公开还提供一线治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。本公开还提供一线治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物，并且在第二治疗阶段向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。另外，本公开还提供本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物在制备用于治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于一线治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物在制备用于一线治疗肿瘤的药物中的用途。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
另一方面，本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段联合使用。本公开还提供本公 开的抗TIM-3抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段和化疗药物联合使用。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段联合使用。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段和化疗药物联合使用。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
另一方面，本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段和化疗药物联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段和化疗药物联合使用。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
另一方面，本公开还提供在受试者中治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的联用药物组合。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括向受试者给予治疗有效量的本公开的联用药物组合。另外，本公开还提供了本公开的联用药物组合在制备用于治疗受试者中肿瘤的药物中的用途。本公开还提供了本公开的联用药物组合在制备用于一线治疗受试者中肿瘤的药物中的用途。另外，本公开还提供了本公开的联用药物组合治疗受试者中肿瘤的用途。本公开还提供了本公开的联用药物组合一线治疗受试者中肿瘤的用途。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，可同时、先后和/或交替给药。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物，可同时、先后和/或交替给药。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用。
在一些实施方案中，所述顺铂每1周、每2周、每3周、或每4周施用一次。在一些实施方案中，所述顺铂每次以30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的剂量施用。
在一些实施方案中，所述卡铂每1周、每2周、每3周、或每4周施用一次。在一些实施方案中，所述卡铂每次以2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的剂量施用。
在一些实施方案中，所述紫杉醇每1周、每2周、每3周、或每4周施用一次。在一些实施方案中，所述紫杉醇每次以75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的剂量施用。
在另一方面，本公开提供用于治疗肿瘤的试剂盒，其包括本公开的药物组合。在一些实施方案中，所述试剂盒包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；任选地，还包括化疗药物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
此外，本公开还提供在受试者中治疗肿瘤的方法，包括向受试者给予治疗有效量的本公开的抗TIM-3抗体或其抗原结合片段。本公开还提供在受试者中一线治疗肿瘤的方法，包括向受试者给予治疗有效量的 本公开的抗TIM-3抗体或其抗原结合片段。本公开还提供抗TIM-3抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途。本公开还提供抗TIM-3抗体或其抗原结合片段治疗肿瘤的用途。
此外，本公开还提供在受试者中治疗肿瘤的方法，包括向受试者给予治疗有效量的本公开的抗PD-1抗体或其抗原结合片段与化疗药物。本公开还提供在受试者中一线治疗肿瘤的方法，包括向受试者给予治疗有效量的本公开的抗PD-1抗体或其抗原结合片段与化疗药物。本公开还提供抗PD-1抗体或其抗原结合片段与化疗药物在制备用于治疗受试者中肿瘤的药物中的用途。本公开还提供抗PD-1抗体或其抗原结合片段与化疗药物治疗肿瘤的用途。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述肿瘤为实体瘤。在一些实施方案中，所述肿瘤为头颈癌。在一些实施方案中，所述肿瘤为食管癌。
发明详述
药物组合
在一方面，本公开提供一种药物组合，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；任选地，还包括化疗药物。
在一些实施方案中，所述化疗药物包括但不限于铂类抗肿瘤药物、紫杉烷类抗肿瘤药物、抗代谢类抗肿瘤药物、喜树碱类抗肿瘤药物、氮芥类抗肿瘤药物、蒽环类抗肿瘤药物、长春碱类抗肿瘤药物、鬼臼生物碱类抗肿瘤药物、和激素类抗肿瘤药物中一种或多种。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和紫杉烷类抗肿瘤药物。在一些具体实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些具体实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述药物组合包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。在一些实施方案中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、铂类抗肿瘤药物和紫杉烷类抗肿瘤药物。在一些实施方案中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇。在另一些实施方案中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇。
此外，本公开还提供了一种联用药物组合，其包含：
(a)本公开的药物组合，其被制备为适合在第一治疗阶段向受试者给予；和
(b)本公开的药物组合，其被制备为适合在第二治疗阶段向受试者给予。
在一些实施方案中，所述联用药物组合包含：
(a)包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物的药物组合，其被制备为适合在第一治疗阶段向受试者给予；和
(b)包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段向受试者给予。
在一些实施方案中，所述联用药物组合包含：
(a)包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、铂类抗肿瘤药物和紫杉烷类抗肿瘤药物的药物组合，其被制备为适合在第一治疗阶段向受试者给予；和
(b)包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段向受试者给予。
在一些实施方案中，所述联用药物组合包含：
(a)包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇的药物组合，其被制备为适合在第一治疗阶段向受试者给予；和
(b)包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段向受试者给予。
在一些实施方案中，所述联用药物组合包含：
(a)包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇的药物组合，其被制备为适合在第一治疗阶段向受试者给予；和
(b)包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段向受试者给予。
在一些实施方案中，所述第一治疗阶段包括1-14个治疗周期，优选2-12个治疗周期、2-10个治疗周期，更优选2-8个治疗周期，例如：2-8个治疗周期，3-8个治疗周期，4-8个治疗周期，2-7个治疗周期，3-7个治疗周期，4-7个治疗周期，2-6个治疗周期，3-6个治疗周期，或4-6个治疗周期；最优选4-6个治疗周期，例如：4个治疗周期，5个治疗周期，和/或6个治疗周期。在一些实施方案中，所述第一治疗阶段包括4个治疗周期。在一些实施方案中，所述第一治疗阶段包括6个治疗周期。
在一些实施方案中，每1周、每2周、每3周、或每4周为一个治疗周期。在一些实施方案中，每3周为一个治疗周期。
在一些实施方案中，所述第二治疗阶段在第一治疗阶段之后。在一些实施方案中，所述第二治疗阶段是从第一治疗阶段结束后持续直到失去临床获益、毒性不可耐受、疗效评价为疾病进展(PD)、和/或研究者认为不适合继续用药。
在一些实施方案中，所述药物组合包装于同一试剂盒中，所述试剂盒还包括将抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段联合使用以治疗肿瘤的说明。在另一些实施方案中，所述药物组合中的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分开包装于各自的药盒中，所述药盒还包括将抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段联合使用以治疗肿瘤的说明。
在一些实施方案中，所述药物组合包装于同一试剂盒中，所述试剂盒还包括将抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)联合使用以治疗肿瘤的说明。在另一些实施方案中，所述药物组合中的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)分开包装于各自的药盒中，所述药盒还包括将抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)联合使用以治疗肿瘤的说明。
在一些实施方案中，所述药物组合是固定组合。在一些实施方案中，所述固定组合中的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。在一些实施方案中，所述固定组合中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物呈液体制剂的形式或固体制剂的形式。在一些具体实施方案中，所述固定组合中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案中，所述固定组合中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述药物组合是非固定组合。在一些实施方案中，所述非固定组合中的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段各自呈药物组合物的形式。在一些实施方案中，所述非固定组合中的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)各自呈药物组合物的形式。
在一些实施方案中，所述非固定组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述非固定组合中，含抗PD-1抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述非固定组合中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。在一些实施方案中，所述非固定组合中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案 中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述非固定组合中，含化疗药物的药物组合物为液体制剂或固体制剂。在一些实施方案中，含顺铂的药物组合物为液体制剂。在一些具体的实施方案中，含顺铂的药物组合物为注射液。在一些实施方案中，含顺铂的药物组合物为固体制剂。在一些具体实施方案中，含顺铂的药物组合物为冻干制剂。在一些具体实施方案中，含顺铂的药物组合物为粉针制剂。在一些实施方案中，含卡铂的药物组合物为液体制剂。在一些具体的实施方案中，含卡铂的药物组合物为注射液。在一些实施方案中，含卡铂的药物组合物为固体制剂。在一些具体实施方案中，含卡铂的药物组合物为冻干制剂。在一些具体实施方案中，含卡铂的药物组合物为粉针制剂。在一些实施方案中，含紫杉醇的药物组合物为液体制剂。在一些具体实施方案中，含紫杉醇的药物组合物为注射液。在一些实施方案中，含紫杉醇的药物组合物为固体制剂。在一些具体实施方案中，含紫杉醇的药物组合物为冻干制剂。在一些具体实施方案中，含紫杉醇的药物组合物为粉针制剂。
本公开的目的还在于提供一种药物包，其在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段的药物组合物，在第二个容器中包括含抗PD-1抗体或其抗原结合片段的药物组合物；任选地，还包含一个或多个其他容器，在其他容器中包括含化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)的药物组合物。
本公开的目的还在于提供一种药物包，其在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物；任选地，还包含一个或多个其他容器，在其他容器中包括含化疗药物(例如，顺铂和紫杉醇，或卡铂和紫杉醇)的药物组合物。
在一些实施方案中，所述药物组合中抗TIM-3抗体或其抗原结合片段的单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg。在一些实施方案中，所述药物组合中抗TIM-3抗体或其抗原结合片段的单位剂量为约60mg、约120mg、约160mg、约180mg、约200mg、约240mg、约280mg、约300mg、约320mg、约360mg、约400mg、约420mg、约440mg、约480mg、约520mg、约540mg、约560mg、约600mg、约640mg、约660mg、约680mg、约720mg、约760mg、约780mg、约800mg、约840mg、约880mg、约900mg、约920mg、约960mg、约1000mg、约1020mg、约1040mg、约1080mg、约1120mg、约1140mg、约1160mg、约1200mg、约1240mg、约1260mg、约1280mg、约1320mg、约1360mg、约1380mg、约1400mg、约1440mg、约1480mg、约1500mg、约1520mg、约1560mg、约1600mg、约1620mg、约1640mg、约1680mg、约1720mg、约1740mg、约1760mg和/或约1800mg、或上述任意值形成的范围。在一些实施方案中，所述药物组合中抗TIM-3抗体或其抗原结合片段的单位剂量为约240mg、约300mg、约360mg和/或约600mg。在一些实施方案中，所述药物组合中抗TIM-3抗体或其抗原结合片段的单位剂量为约240mg和/或约600mg。
在一些实施方案中，所述药物组合中抗PD-1抗体或其抗原结合片段的单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg。在一些实施方案中，所述药物组合中抗PD-1抗体或其抗原结合片段的单位剂量为约10mg、约20mg、约30mg、约40mg、约50mg、约60mg、约70mg、约80mg、约90mg、约100mg、约110mg、约120mg、约130mg、约140mg、约150mg、约160mg、约170mg、约180mg、约190mg、约200mg、约210mg、约220mg、约230mg、约240mg、约250mg、约260mg、约270mg、约280mg、约290mg、约300mg、约310mg、约320mg、约330mg、约340mg、约350mg、约360mg、约370mg、约380mg、约390mg、约400mg、约410mg、约420mg、约430mg、约440mg、约450mg、约460mg、约470mg、约480mg、约490mg和/或约500mg、或上述任意值形成的范围。在一些实施方案中，所述药物组合中抗PD-1抗体或其抗原结合片段的单位剂量为约100mg和/或约200mg。在一些实施方案中，所述药物组合中抗PD-1抗体或其抗原结合片段的单位剂量为约100mg。
在一些实施方案中，所述药物组合还包括化疗药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些实施方案中，所述药物组合中顺铂的单位剂量为1-200mg或2.5-100mg。在一些实施方案中，所述药物组合中顺铂的单位剂量为2.5mg、5mg、10mg、20mg、25mg、30mg、50mg和/或100mg。在一些实施方案中，所述药物组合中顺铂的单位剂量为10mg、20mg、30mg、50mg和/或100mg。在一些实施方案中，所述药物组合中卡铂的单位剂量为10- 500mg或50-450mg。在一些实施方案中，所述药物组合中卡铂的单位剂量为50mg、100mg、150mg、250mg和/或450mg。在一些实施方案中，所述药物组合中紫杉醇的单位剂量为10-300mg或30-150mg。在一些实施方案中，所述药物组合中紫杉醇的单位剂量为30mg、60mg、100mg和/或150mg。
在一些实施方案中，所述药物组合包括单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg的抗TIM-3抗体或其抗原结合片段，和单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括单位剂量为约60mg、约120mg、约160mg、约180mg、约200mg、约240mg、约280mg、约300mg、约320mg、约360mg、约400mg、约420mg、约440mg、约480mg、约520mg、约540mg、约560mg、约600mg、约640mg、约660mg、约680mg、约720mg、约760mg、约780mg、约800mg、约840mg、约880mg、约900mg、约920mg、约960mg、约1000mg、约1020mg、约1040mg、约1080mg、约1120mg、约1140mg、约1160mg、约1200mg、约1240mg、约1260mg、约1280mg、约1320mg、约1360mg、约1380mg、约1400mg、约1440mg、约1480mg、约1500mg、约1520mg、约1560mg、约1600mg、约1620mg、约1640mg、约1680mg、约1720mg、约1740mg、约1760mg和/或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，和单位剂量为约10mg、约20mg、约30mg、约40mg、约50mg、约60mg、约70mg、约80mg、约90mg、约100mg、约110mg、约120mg、约130mg、约140mg、约150mg、约160mg、约170mg、约180mg、约190mg、约200mg、约210mg、约220mg、约230mg、约240mg、约250mg、约260mg、约270mg、约280mg、约290mg、约300mg、约310mg、约320mg、约330mg、约340mg、约350mg、约360mg、约370mg、约380mg、约390mg、约400mg、约410mg、约420mg、约430mg、约440mg、约450mg、约460mg、约470mg、约480mg、约490mg和/或约500mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括单位剂量为约240mg、约300mg、约360mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，和单位剂量为约100mg和/或约200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括单位剂量为约240mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，和单位剂量为约100mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，所述药物组合还包括单位剂量为1-200mg或2.5-100mg的顺铂，和单位剂量为10-300mg或30-150mg的紫杉醇。在一些实施方案中，所述药物组合还包括单位剂量为2.5mg、5mg、10mg、20mg、25mg、30mg、50mg和/或100mg的顺铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。在一些实施方案中，所述药物组合还包括单位剂量为10mg、20mg、30mg、50mg和/或100mg的顺铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。
在另一些实施方案中，所述药物组合还包括单位剂量为10-500mg或50-450mg的卡铂，和单位剂量为10-300mg或30-150mg的紫杉醇。在另一些实施方案中，所述药物组合还包括单位剂量为50mg、100mg、150mg、250mg和/或450mg的卡铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。
在一些具体的实施方案中，所述药物组合包括单位剂量为约240mg、约300mg、约360mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，单位剂量为约100mg和/或约200mg的抗PD-1抗体或其抗原结合片段，单位剂量为10mg、20mg、30mg、50mg和/或100mg的顺铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。在一些具体的实施方案中，所述药物组合包括单位剂量为约240mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，单位剂量为约100mg的抗PD-1抗体或其抗原结合片段，单位剂量为10mg、20mg、30mg、50mg和/或100mg的顺铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。
在另一些具体的实施方案中，所述药物组合包括单位剂量为约240mg、约300mg、约360mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，单位剂量为约100mg和/或约200mg的抗PD-1抗体或其抗原结合片段，单位剂量为50mg、100mg、150mg、250mg和/或450mg的卡铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。在另一些具体的实施方案中，所述药物组合包括单位剂量为约240mg和/或约600mg的抗TIM-3抗体或其抗原结合片段，单位剂量为约100mg的抗PD-1抗体或其抗原结合片段，单位剂量为50mg、100mg、150mg、250mg和/或450mg的卡铂，和单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。
在一些实施方案中，所述药物组合包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段。
在一些实施方案中，所述药物组合包括10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约200mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，所述药物组合还包括化疗药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些实施方案中，所述药物组合还包括30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，或者2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合还包括约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的顺铂，或者约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂。在一些实施方案中，所述药物组合还包括48-75mg/m2的顺铂，或者3.2-5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合还包括约48mg/m2、约60mg/m2或约75mg/m2的顺铂，或者约3.2mg/(mL/min)AUC、约4mg/(mL/min)AUC或约5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合还包括约75mg/m2的顺铂，或者约5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合还包括30-75mg/m2的顺铂。在一些实施方案中，所述药物组合还包括60-75mg/m2的顺铂。在一些实施方案中，所述药物组合还包括约60mg/m2的顺铂。在一些实施方案中，所述药物组合还包括约75mg/m2的顺铂。在一些实施方案中，所述药物组合还包括75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在一些实施方案中，所述药物组合还包括112-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约112mg/m2、约135mg/m2、约140mg/m2、约150mg/m2或约175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括67.5-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括135-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约135mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约150mg/m2的紫杉醇。
在一些实施方案中，所述药物组合包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，和10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，和约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约1200mg或约1500mg 的抗TIM-3抗体或其抗原结合片段，和约200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段，和约200mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，所述药物组合还包括30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的顺铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在一些实施方案中，所述药物组合还包括48-75mg/m2的顺铂，和112-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约75mg/m2的顺铂，和约175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括30-75mg/m2的顺铂，和67.5-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括60-75mg/m2的顺铂，和135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合还包括约60mg/m2或约75mg/m2的顺铂，和约135mg/m2或约150mg/m2的紫杉醇。
在另一些实施方案中，所述药物组合还包括2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在另一些实施方案中，所述药物组合还包括约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在另一些实施方案中，所述药物组合还包括3.2-5mg/(mL/min)AUC的卡铂，和112-175mg/m2的紫杉醇。在另一些实施方案中，所述药物组合还包括约5mg/(mL/min)AUC的卡铂，和约175mg/m2的紫杉醇。
在一些实施方案中，所述药物组合还包括顺铂和紫杉醇。在一些具体的实施方案中，所述药物组合包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，48-75mg/m2的顺铂，和112-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，约75mg/m2的顺铂，和约175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，30-75mg/m2的顺铂，和67.5-150mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，约60mg/m2或约75mg/m2的顺铂，和约135mg/m2或约150mg/m2的紫杉醇。
在另一些实施方案中，所述药物组合还包括卡铂和紫杉醇。在另一些具体的实施方案中，所述药物组合包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，2.5-5mg/(mL/min)AUC或3.2- 5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在另一些具体的实施方案中，所述药物组合包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，3.2-5mg/(mL/min)AUC的卡铂，和112-175mg/m2的紫杉醇。在另一些具体的实施方案中，所述药物组合包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，约5mg/(mL/min)AUC的卡铂，和约175mg/m2的紫杉醇。
在一些实施方案中，所述药物组合中，抗TIM-3抗体或其抗原结合片段的含量为一日剂量。在一些实施方案中，所述药物组合中，抗TIM-3抗体或其抗原结合片段的含量为一日一次剂量。
在一些实施方案中，所述药物组合中，抗TIM-3抗体或其抗原结合片段的含量为统一剂量。
在一些实施方案中，所述药物组合中，抗TIM-3抗体或其抗原结合片段的含量为一个治疗周期的剂量，每个治疗周期为3周。
在一些实施方案中，所述药物组合中，抗PD-1抗体或其抗原结合片段的含量为一日剂量。在一些实施方案中，所述药物组合中，抗PD-1抗体或其抗原结合片段的含量为一日一次剂量。
在一些实施方案中，所述药物组合中，抗PD-1抗体或其抗原结合片段的含量为统一剂量。
在一些实施方案中，所述药物组合中，抗PD-1抗体或其抗原结合片段的含量为一个治疗周期的剂量，每个治疗周期为3周。
在一些实施方案中，所述药物组合中，顺铂的含量为一日剂量。在一些实施方案中，所述药物组合中，顺铂的含量为一日一次剂量。
在一些实施方案中，所述药物组合中，顺铂的含量为一个治疗周期的剂量，每个治疗周期为3周。
在一些实施方案中，所述药物组合中，卡铂的含量为一日剂量。在一些实施方案中，所述药物组合中，卡铂的含量为一日一次剂量。
在一些实施方案中，所述药物组合中，卡铂的含量为一个治疗周期的剂量，每个治疗周期为3周。
在一些实施方案中，所述药物组合中，紫杉醇的含量为一日剂量。在一些实施方案中，所述药物组合中，紫杉醇的含量为一日一次剂量。
在一些实施方案中，所述药物组合中，紫杉醇的含量为一个治疗周期的剂量，每个治疗周期为3周。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约200mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括化疗药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，或者2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意 值形成的范围的顺铂，或者约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括48-75mg/m2的顺铂，或者3.2-5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括48mg/m2、约60mg/m2或约75mg/m2的顺铂，或者约3.2mg/(mL/min)AUC、约4mg/(mL/min)AUC或约5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约75mg/m2的顺铂，或者约5mg/(mL/min)AUC的卡铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括30-75mg/m2的顺铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括60-75mg/m2的顺铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约60mg/m2的顺铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约75mg/m2的顺铂。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括112-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约112mg/m2、约135mg/m2、约140mg/m2、150mg/m2或约175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括67.5-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括135-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约135mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约150mg/m2的紫杉醇。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，和10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，和约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，和约200mg的抗PD-1抗体或其抗原结合片段。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段，和约200mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的顺铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括48-75mg/m2的顺铂，和112-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括75mg/m2的顺铂、和175mg/m2的紫杉醇。在一些实施方案中，所述药物 组合适用于在单个治疗周期内施用，还包括30-75mg/m2的顺铂，和67.5-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括60-75mg/m2的顺铂、和135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括60-75mg/m2的顺铂、和135-150mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约60mg/m2或约75mg/m2的顺铂、和约135mg/m2或约150mg/m2的紫杉醇。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括3.2-5mg/(mL/min)AUC的卡铂，和112-175mg/m2的紫杉醇。在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，还包括5mg/(mL/min)AUC的卡铂、和175mg/m2的紫杉醇。
在一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，48-75mg/m2的顺铂，和112-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，75mg/m2的顺铂，和175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，30-75mg/m2的顺铂，和67.5-150mg/m2的紫杉醇。一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-175mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇。在一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇。在另一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，约60mg/m2或约75mg/m2的顺铂，和约135mg/m2或约150mg/m2的紫杉醇。
在另一些实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇。在另一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在另一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，3.2-5mg/(mL/min)AUC的卡铂，和112-175mg/m2的紫杉醇。在另一些具体的实施方案中，所述药物组合适用于在单个治疗周期内施用，其包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，5mg/(mL/min)AUC的卡铂，和175mg/m2的紫杉醇。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，和10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段，约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的顺铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，和约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，48-75mg/m2的顺铂，和112-175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，75mg/m2的顺铂，和175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，30-75mg/m2的顺铂，和67.5-150mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，60-75mg/m2的顺铂，和135-150mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，约60mg/m2或约75mg/m2的顺铂，和约135mg/m2或约150mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，和10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段，约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂，和约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600 mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段，和约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，3.2-5mg/(mL/min)AUC的卡铂，和112-175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，本公开提供的联用药物组合包含：
(a)包括约1200mg的抗TIM-3抗体或其抗原结合片段，约200mg的抗PD-1抗体或其抗原结合片段，5mg/(mL/min)AUC的卡铂，和175mg/m2的紫杉醇的药物组合，其被制备为适合在第一治疗阶段的单个治疗周期向受试者给予；和
(b)包括约1200mg的抗TIM-3抗体或其抗原结合片段和约200mg的抗PD-1抗体或其抗原结合片段的药物组合，其被制备为适合在第二治疗阶段的单个治疗周期向受试者给予。
在一些实施方案中，所述第一治疗阶段包括1-14个治疗周期，优选2-12个治疗周期、2-10个治疗周期，更优选2-8个治疗周期，例如：2-8个治疗周期，3-8个治疗周期，4-8个治疗周期，2-7个治疗周期，3-7个治疗周期，4-7个治疗周期，2-6个治疗周期，3-6个治疗周期，或4-6个治疗周期；最优选4-6个治疗周期，例如：4个治疗周期，5个治疗周期，和/或6个治疗周期。在一些实施方案中，所述第一治疗阶段包括4个治疗周期。在一些实施方案中，所述第一治疗阶段包括6个治疗周期。
在一些实施方案中，每1周、每2周、每3周、或每4周为一个治疗周期。在一些实施方案中，每3周为一个治疗周期。
在一些实施方案中，所述第二治疗阶段在第一治疗阶段之后。在一些实施方案中，所述第二治疗阶段是从第一治疗阶段结束后持续直到失去临床获益、毒性不可耐受、疗效评价为PD、和/或研究者认为不适合继续用药。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段可以是含抗TIM-3抗体或其抗原结合片段的药物组合物。其中，含抗TIM-3抗体或其抗原结合片段的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述多剂量可以由单剂量为含约240mg、约300mg、约360mg和/或约600mg抗TIM-3抗体或其抗原结合片段的药物组合物组成。在一些实施方案中，所述多剂量可以由单剂量为含约240mg和/或约600mg抗TIM-3抗体或其抗原结合片段的药物组合物组成。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段可以是含抗PD-1抗体或其抗原结合片段的药物组合物。其中，含抗PD-1抗体或其抗原结合片段的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述多剂量可以由单剂量为含约100mg和/或约200mg抗PD-1抗体或其抗原结合片段的药物组合物组成。在一些实施方案中，所述多剂量可以由单剂量为含约100mg抗PD-1抗体或其抗原结合片段的药物组合物组成。
在一些实施方案中，所述化疗药物可以是含化疗药物的药物组合物。其中，含化疗药物的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述顺铂可以是含顺铂的药物组合物。其中，含顺铂的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述多剂量可以由单剂量为含2.5mg、5mg、10mg、20mg、25mg、30mg、50mg和/或100mg顺铂的药物组合物组成。在一些实施方案中，所述多剂量可以由单剂量为含10mg、20mg、30mg、50mg和/或100mg顺铂的药物组合物组成。
在一些实施方案中，所述卡铂可以是含卡铂的药物组合物。其中，含卡铂的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述多剂量可以由单剂量为含50mg、100mg、150mg、250mg 和/或450mg卡铂的药物组合物组成。
在一些实施方案中，所述紫杉醇可以是含紫杉醇的药物组合物。其中，含紫杉醇的药物组合物为单剂量或多剂量，优选为多剂量。在一些实施方案中，所述多剂量可以由单剂量为含30mg、60mg、100mg和/或150mg紫杉醇的药物组合物组成。
在一些实施方案中，所述药物组合中，所述抗TIM-3抗体或其抗原结合片段:抗PD-1抗体或其抗原结合片段的质量比为(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1；其中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段可分开包装或包装在一起。在一些实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分开包装，其中，抗TIM-3抗体或其抗原结合片段能够以单份或多份进行包装，抗PD-1抗体或其抗原结合片段能够以单份或多份进行包装。在一些实施方案中，抗TIM-3抗体或其抗原结合片段能够以单份或多个等份(例如2等份、3等份、4等份、5等份、6等份、7等份、8等份或更多等份)进行包装，抗PD-1抗体或其抗原结合片段能够以单份或多个等份(例如2等份或其他等份)进行包装。
在一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物，其中含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予100-1800mg、600-1800mg、600-1500mg、或1200-1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予10-800mg、50-500mg、或100-200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量。在一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物，其中含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段的单剂量或多剂量。在一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物，其中含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量。在一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物，其中含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量。
在一些实施方案中，所述药物组合还包括化疗药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇的单剂量或多剂量。在一些实施方案中，所 述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予48-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予112-175mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予175mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予30-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予67.5-150mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予135-175mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予135-150mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含顺铂的药物组合物和含紫杉醇的药物组合物，其中含顺铂的药物组合物被制备为适合向患者给予约60mg/m2或约75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予约135mg/m2或约150mg/m2紫杉醇的单剂量或多剂量。
在另一些实施方案中，所述药物组合还包括含卡铂的药物组合物和含紫杉醇的药物组合物，其中含卡铂的药物组合物被制备为适合向患者给予2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2紫杉醇的单剂量或多剂量。在另一些实施方案中，所述药物组合还包括含卡铂的药物组合物和含紫杉醇的药物组合物，其中含卡铂的药物组合物被制备为适合向患者给予约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含卡铂的药物组合物和含紫杉醇的药物组合物，其中含卡铂的药物组合物被制备为适合向患者给予3.2-5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予112-175mg/m2紫杉醇的单剂量或多剂量。在一些实施方案中，所述药物组合还包括含卡铂的药物组合物和含紫杉醇的药物组合物，其中含卡铂的药物组合物被制备为适合向患者给予5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予175mg/m2紫杉醇的单剂量或多剂量。
在一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物、含顺铂的药物组合物、和含紫杉醇的药物组合物。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予100-1800mg、600-1800mg、600-1500mg、或1200-1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予10-800mg、50-500mg、或100-200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予48-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予112-175mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适 合向患者给予约1200mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予175mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予30-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予67.5-150mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予135-175mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予135-150mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予60-75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予135-150mg/m2紫杉醇的单剂量或多剂量。在一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含顺铂的药物组合物被制备为适合向患者给予约60mg/m2或约75mg/m2顺铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予约135mg/m2或约150mg/m2紫杉醇的单剂量或多剂量。
在另一些实施方案中，所述药物组合包括含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物、含卡铂的药物组合物、和含紫杉醇的药物组合物。在另一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约100-1800mg、600-1800mg、600-1500mg、或1200-1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予10-800mg、50-500mg、或100-200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含卡铂的药物组合物被制备为适合向患者给予2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2紫杉醇的单剂量或多剂量。在另一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含卡铂的药物组合物被制备为适合向患者给予3.2-5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予112-175mg/m2紫杉醇的单剂量或多剂量。在另一些具体的实施方案中，所述药物组合中，含抗TIM-3抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约1200mg抗TIM-3抗体或其抗原结合片段的单剂量或多剂量，含抗PD-1抗体或其抗原结合片段的药物组合物被制备为适合向患者给予约200mg抗PD-1抗体或其抗原结合片段的单剂量或多剂量，含卡铂的药物组合物被制备为适合向患者给予5mg/(mL/min)AUC的卡铂的单剂量或多剂量，含紫杉醇的药物组合物被制备为适合向患者给予175mg/m2紫杉醇的单剂量或多剂量。
在另一方面，本公开提供用于治疗肿瘤的试剂盒，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物，以及将含抗TIM-3抗体或其抗原结合片段的药物组合物和含抗PD-1抗体或其抗原结合片段的药物组合物联合使用以治疗肿瘤的说明。
在另一些实施方案中，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物和含化疗药物的药物组合物，以及将含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物和含化疗药物的药物组合物联合使用以治疗肿瘤的说明。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些具体的实施方案中，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物、含顺铂或卡铂的药物组合物、和含紫杉醇的药物组合物，以及将含抗TIM-3抗体或其抗原结合片段的药物组合物、含抗PD-1抗体或其抗原结合片段的药物组合物、含顺铂或卡铂的药物组合物和含紫杉醇的药物组合物联合使用以治疗肿瘤的说明。
在另一方面，本公开提供用于治疗肿瘤的试剂盒，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物，以及使用所述药物组合物治疗肿瘤的说明。
在另一些实施方案中，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物和含化疗药物的药物组合物，以及将含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物、和含化疗药物的药物组合物联合使用以治疗肿瘤的说明。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些具体的实施方案中，所述试剂盒包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物、含顺铂或卡铂的药物组合物、和含紫杉醇的药物组合物，以及将含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物、含顺铂或卡铂的药物组合物、和含紫杉醇的药物组合物联合使用以治疗肿瘤的说明。
在另一方面，本公开还提供用于治疗肿瘤的药物包，其在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段的药物组合物，在第二个容器中包括含抗PD-1抗体或其抗原结合片段的药物组合物；任选地，还包含一个或多个其他容器，在其他容器中包括含化疗药物的药物组合物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些具体实施方案中，所述药物包在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段的药物组合物，并在第二个容器中包括含抗PD-1抗体或其抗原结合片段的药物组合物。在一些具体实施方案中，所述药物包在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段的药物组合物，在第二个容器中包括含抗PD-1抗体或其抗原结合片段的药物组合物，在第三个容器中包括含顺铂或卡铂的药物组合物，并在第四个容器中包括含紫杉醇的药物组合物。
在另一方面，本公开还提供用于治疗肿瘤的药物包，其在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物；任选地，还包含一个或多个其他容器，在其他容器中包括含化疗药物的药物组合物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些实施方案中，所述化疗药物为卡铂和紫杉醇。在一些具体实施方案中，所述药物包在独立的容器中包含单包装的药物组合物，其中，在所述容器中包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物。在一些具体实施方案中，所述药物包在独立的容器中分别包含单包装的药物组合物，其中，在第一个容器中包括含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物，在第二个容器中包括含顺铂或卡铂的药物组合物，并在第三个容器中包括含紫杉醇的药物组合物。
在一些实施方案中，所述试剂盒或药物包中，含抗TIM-3抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为注射液。在 一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述试剂盒或药物包中，含抗PD-1抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述试剂盒或药物包中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为注射液。在一些具体实施方案中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。
在一些实施方案中，所述试剂盒或药物包中，含化疗药物的药物组合物为液体制剂或固体制剂。在一些具体实施方案中，所述试剂盒或药物包中，含顺铂的药物组合物为液体制剂。在一些具体实施方案中，含顺铂的药物组合物为注射液。在一些实施方案中，含顺铂的药物组合物为固体制剂。在一些具体实施方案中，含顺铂的药物组合物为冻干制剂。在一些具体实施方案中，含顺铂的药物组合物为粉针制剂。在一些具体实施方案中，所述试剂盒或药物包中，含卡铂的药物组合物为液体制剂。在一些具体实施方案中，含卡铂的药物组合物为注射液。在一些实施方案中，含卡铂的药物组合物为固体制剂。在一些具体实施方案中，含卡铂的药物组合物为冻干制剂。在一些具体实施方案中，含卡铂的药物组合物为粉针制剂。在一些具体实施方案中，所述试剂盒或药物包中，含紫杉醇的药物组合物为液体制剂。在一些具体实施方案中，含紫杉醇的药物组合物为注射液。在一些实施方案中，含紫杉醇的药物组合物为固体制剂。在一些具体实施方案中，含紫杉醇的药物组合物为冻干制剂。在一些具体实施方案中，含紫杉醇的药物组合物为粉针制剂。
在一些实施方案中，所述肿瘤为实体瘤。在一些实施方案中，所述实体瘤为头颈癌。在一些实施方案中，所述实体瘤为食管癌。
用途
本公开还提供在受试者中治疗肿瘤的方法，其包括向受试者给予本公开的药物组合。本公开提供在受试者中一线治疗肿瘤的方法，其包括向受试者给予本公开的药物组合。本公开还提供在受试者中治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予本公开的药物组合，并且在第二治疗阶段向受试者给予本公开的药物组合。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括向受试者给予本公开的药物组合。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予本公开的药物组合，并且在第二治疗阶段向受试者给予本公开的药物组合。
另一方面，本公开还提供了本公开的药物组合在制备用于治疗受试者中肿瘤的药物中的用途。本公开还提供了本公开的药物组合在制备用于一线治疗受试者中肿瘤的药物中的用途。另外，本公开还提供了本公开的药物组合治疗受试者中肿瘤的用途。本公开还提供了本公开的药物组合一线治疗受试者中肿瘤的用途。在一些实施方案中，所述用途包括向受试者给予本公开的药物组合。在一些实施方案中，所述用途包括在第一治疗阶段向受试者给予本公开的药物组合，并且在第二治疗阶段向受试者给予本公开的药物组合。
另一方面，本公开还提供治疗肿瘤的方法，其包括向受试者给予本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。本公开还提供治疗肿瘤的方法，其包括向受试者给予本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。本公开还提供一线治疗肿瘤的方法，其包括向受试者给予本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。本公开还提供一线治疗肿瘤的方法，其包括向受试者给予本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。在一些具体的实施方案中，本公开提供在受试者中一线治疗肿瘤的方法，其包括在第一治疗阶段向受试者给予本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物，并且在第二治疗阶段向受试者给予本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。另外，本公开还提供本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物在制备用于治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于一线治疗肿瘤的药物中的用途。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合 片段和化疗药物在制备用于一线治疗肿瘤的药物中的用途。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
另一方面，本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段联合使用。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段和化疗药物联合使用。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段联合使用。本公开还提供本公开的抗TIM-3抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗PD-1抗体或其抗原结合片段和化疗药物联合使用。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
另一方面，本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段和化疗药物联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段联合使用。本公开还提供本公开的抗PD-1抗体或其抗原结合片段在制备用于一线治疗受试者中肿瘤的药物中的用途，其中所述药物用于与本公开的抗TIM-3抗体或其抗原结合片段和化疗药物联合使用。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为顺铂和紫杉醇。在一些实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，在所述方法或用途中，所述药物组合包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。在一些实施方案中，在所述方法或用途中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物。在一些实施方案中，所述化疗药物包括但不限于铂类抗肿瘤药物、紫杉烷类抗肿瘤药物、抗代谢类抗肿瘤药物、喜树碱类抗肿瘤药物、氮芥类抗肿瘤药物、蒽环类抗肿瘤药物、长春碱类抗肿瘤药物、鬼臼生物碱类抗肿瘤药物、和激素类抗肿瘤药物中一种或多种。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些具体实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些具体实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，在所述方法或用途中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、铂类抗肿瘤药物和紫杉烷类抗肿瘤药物。在一些实施方案中，在所述方法或用途中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇。在另一些实施方案中，在所述方法或用途中，所述药物组合包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇。
在一些实施方案中，在所述方法或用途中，其包括在第一治疗阶段向受试者给予治疗有效量的本公开的药物组合，并且在第二治疗阶段向受试者给予治疗有效量的本公开的药物组合。
在一些实施方案中，在所述方法或用途中，其包括在第一治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物的药物组合；并且
在第二治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合。
在一些实施方案中，在所述方法或用途中，其包括在第一治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、铂类抗肿瘤药物和紫杉烷类抗肿瘤药物的药物组合；并且
在第二治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合。
在一些实施方案中，在所述方法或用途中，其包括在第一治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇的药物组合；并且
在第二治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合。
在一些实施方案中，在所述方法或用途中，其包括在第一治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇的药物组合；并且
在第二治疗阶段向受试者给予治疗有效量的包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合。
在一些实施方案中，所述第一治疗阶段包括1-14个治疗周期，优选2-12个治疗周期、2-10个治疗周期，更优选2-8个治疗周期，例如：2-8个治疗周期，3-8个治疗周期，4-8个治疗周期，2-7个治疗周期，3-7个治疗周期，4-7个治疗周期，2-6个治疗周期，3-6个治疗周期，或4-6个治疗周期；最优选4-6个治疗周期，例如：4个治疗周期，5个治疗周期，和/或6个治疗周期。在一些实施方案中，所述第一治疗阶段包括4个治疗周期。在一些实施方案中，所述第一治疗阶段包括6个治疗周期。
在一些实施方案中，每1周、每2周、每3周、或每4周为一个治疗周期。在一些实施方案中，每3周为一个治疗周期。
在一些实施方案中，所述第二治疗阶段在第一治疗阶段之后。在一些实施方案中，所述第二治疗阶段是从第一治疗阶段结束后持续直到失去临床获益、毒性不可耐受、疗效评价为PD、研究者认为不适合继续用药。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段同时给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段各自呈药物组合物的形式，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段各自呈药物组合物的形式，先后给药。在一些实施方案中，在所述方法或用途中，先施用抗PD-1抗体或其抗原结合片段，再施用抗TIM-3抗体或其抗原结合片段。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段各自呈药物组合物的形式，先施用含抗PD-1抗体或其抗原结合片段的药物组合物，再施用含抗TIM-3抗体或其抗原结合片段的药物组合物。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中，同时给药。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、和化疗药物，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、和化疗药物各自呈药物组合物的形式，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇，先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇各自呈药物组合物的形式，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇各自呈药物组合物的形式，先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中，所述单一制剂、顺铂和紫杉醇各自呈药物组合物的形式，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中，所述单一制剂、顺铂和紫杉醇各自呈药物组合物的形式，先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇，先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇各自呈药物组合物的形式，可同 时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇各自呈药物组合物的形式，先后给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中，所述单一制剂、卡铂和紫杉醇各自呈药物组合物的形式，可同时、先后和/或交替给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中，所述单一制剂、卡铂和紫杉醇各自呈药物组合物的形式，先后给药。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分别以相同或不同的给药方案进行给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分别以不同的给药方案进行给药。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物分别以相同或不同的给药方案进行给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇分别以相同或不同的给药方案进行给药。在一些具体的实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇分别以不同的给药方案进行给药。在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇分别以相同或不同的给药方案进行给药。在一些具体的实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇分别以不同的给药方案进行给药。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段每1周(q1w)、每2周(q2w)、每3周(q3w)、或每4周(q4w)施用一次。在一个具体的实施方案中，抗TIM-3抗体或其抗原结合片段每3周施用一次。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每次以约100mg、约200mg、约300mg、约400mg、约500mg、约600mg、约700mg、约800mg、约900mg、约1000mg、约1100mg、约1200mg、约1300mg、约1400mg、约1500mg、约1600mg、约1700mg或约1800mg、或上述任意值形成的范围的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每次以约1200mg或约1500mg的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每次以约1200mg的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg抗TIM-3抗体或其抗原结合片段的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，每次以1200-1500mg抗TIM-3抗体或其抗原结合片段的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，每次以约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每3周施用一次，每次以约1200mg或约1500mg抗TIM-3抗体或其抗原结合片段的剂量施用。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段每3周施用一次，每次以约1200mg抗TIM-3抗体或其抗原结合片段的剂量施用。
在一些实施方案中，在所述方法或用途中，所述抗PD-1抗体或其抗原结合片段每1周(q1w)、每2周(q2w)、每3周(q3w)、或每4周(q4w)施用一次。在一个具体的实施方案中，抗PD-1抗体或其抗原结合片段每3周施用一次。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每次以约10mg、约50mg、约100mg、约120mg、约140mg、约160mg、约180mg、约200mg、约220mg、约240mg、约260mg、约280mg、约300mg、约350mg、约400mg、约450mg、约500mg、约550mg、约600mg、约650mg、约700mg、约750mg或约800mg、或上述任意值形成的范围的剂量施用。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每次以约200mg的剂量施用。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，每次以10-800mg、50-500mg、或100-200mg抗PD-1抗体或其抗原结合片段的剂量施用。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，每次以约200mg抗PD-1抗体或其抗 原结合片段的剂量施用。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段每3周施用一次，每次以约200mg抗PD-1抗体或其抗原结合片段的剂量施用。
在一些实施方案中，在所述方法或用途中，所述顺铂每1周(q1w)、每2周(q2w)、每3周(q3w)、或每4周(q4w)施用一次。在一些实施方案中，在所述方法或用途中，所述顺铂每3周(q3w)施用一次。在一些实施方案中，所述顺铂每次以30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的剂量施用。在一些实施方案中，所述顺铂每次以约30mg/m2、约32mg/m2、约35mg/m2、约37mg/m2、约40mg/m2、约45mg/m2、约48mg/m2、约50mg/m2、约52mg/m2、约54mg/m2、约56mg/m2、约60mg/m2、约65mg/m2、约70mg/m2、约75mg/m2、约80mg/m2、约90mg/m2或约100mg/m2、或上述任意值形成的范围的剂量施用。在一些实施方案中，所述顺铂每次以48-75mg/m2的剂量施用。在一些实施方案中，所述顺铂每次以30-75mg/m2的剂量施用。在一些实施方案中，所述顺铂每次以60-75mg/m2的剂量施用。一些实施方案中，所述顺铂每3周施用一次，每次以48-75mg/m2顺铂的剂量施用。在一些实施方案中，所述顺铂每3周施用一次，每次以30-75mg/m2顺铂的剂量施用。在一些实施方案中，所述顺铂每3周施用一次，每次以60-75mg/m2顺铂的剂量施用。在在一些实施方案中，所述顺铂每3周施用一次，每次以约75mg/m2顺铂的剂量施用。在一些实施方案中，所述顺铂每3周施用一次，每次以约60mg/m2或约75mg/m2顺铂的剂量施用。
在一些实施方案中，在所述方法或用途中，所述卡铂每1周(q1w)、每2周(q2w)、每3周(q3w)、或每4周(q4w)施用一次。在一些实施方案中，在所述方法或用途中，所述卡铂每3周(q3w)施用一次。在一些实施方案中，所述卡铂每次以2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的剂量施用。在一些实施方案中，所述卡铂每次以约2.5mg/(mL/min)AUC、约3mg/(mL/min)AUC、约3.2mg/(mL/min)AUC、约3.5mg/(mL/min)AUC、约3.75mg/(mL/min)AUC、约4mg/(mL/min)AUC、约4.5mg/(mL/min)AUC或约5mg/(mL/min)AUC、或上述任意值形成的范围的卡铂的剂量施用。在一些实施方案中，所述卡铂每次以3.2-5mg/(mL/min)AUC的剂量施用。在一些实施方案中，所述卡铂每次以5mg/(mL/min)AUC的剂量施用。在一些实施方案中，所述卡铂每3周施用一次，每次以3.2-5mg/(mL/min)AUC的剂量施用。在一些实施方案中，所述卡铂每3周施用一次，每次以5mg/(mL/min)AUC的剂量施用。
在一些实施方案中，在所述方法或用途中，所述紫杉醇每1周(q1w)、每2周(q2w)、每3周(q3w)、或每4周(q4w)施用一次。在一些实施方案中，在所述方法或用途中，所述紫杉醇每3周(q3w)施用一次。在一些实施方案中，所述紫杉醇滨每次以75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的剂量施用。在一些实施方案中，所述紫杉醇每次以约75mg/m2、约90mg/m2、约100mg/m2、约105mg/m2、约109mg/m2、约112mg/m2、约135mg/m2、约140mg/m2、约145mg/m2、约150mg/m2或约175mg/m2、或上述任意值形成的范围的剂量施用。在一些实施方案中，所述紫杉醇每次以112-175mg/m2的剂量施用。在一些实施方案中，所述紫杉醇每次以67.5-150mg/m2的剂量施用。在一些实施方案中，所述紫杉醇每次以135-150mg/m2的剂量施用。在一些实施方案中，所述紫杉醇每3周施用一次，每次以112-175mg/m2紫杉醇的剂量施用。在一些实施方案中，所述紫杉醇每3周施用一次，每次以67.5-150mg/m2紫杉醇的剂量施用。在一些实施方案中，所述紫杉醇每3周施用一次，每次以135-150mg/m2紫杉醇的剂量施用。在一些实施方案中，所述紫杉醇每3周施用一次，每次以约175mg/m2紫杉醇的剂量施用。在一些实施方案中，所述紫杉醇每3周施用一次，每次以约135mg/m2或约150mg/m2紫杉醇的剂量施用。
在一些实施方案中，在所述方法或用途中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分别具有相同或不同的治疗周期。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段具有相同的治疗周期，例如每1周、每2周、每3周、或每4周为一个治疗周期。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段具有相同的治疗周期，例如每3周为一个治疗周期。
在一些实施方案中，在所述方法或用途中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、和化疗药物分别具有相同或不同的治疗周期。在一些实施方案中，在所述方法或用途中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇分别具有相同或不同的治疗周期。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇具有相同的治疗周期，例如每1周、每2周、每3周、或每4周为一个治疗周期。在一些具体的 实施方案中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇具有相同的治疗周期，例如每3周为一个治疗周期。在一些实施方案中，在所述方法或用途中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇分别具有相同或不同的治疗周期。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇具有相同的治疗周期，例如每1周、每2周、每3周、或每4周为一个治疗周期。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇具有相同的治疗周期，例如每3周为一个治疗周期。
在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期分别给予抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段一次。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予抗TIM-3抗体或其抗原结合片段，在每个治疗周期第1天给予抗PD-1抗体或其抗原结合片段。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予抗TIM-3抗体或其抗原结合片段一次，在每个治疗周期第1天给予抗PD-1抗体或其抗原结合片段一次。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。在这些实施方案中，每3周为一个治疗周期，在每个治疗周期给予所述单一制剂。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期给予所述单一制剂一次。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期第1天给予所述单一制剂。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期第1天给予所述单一制剂一次。
在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段。
在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、和化疗药物。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇。或者，每3周为一个治疗周期，在每个治疗周期给予抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期分别给予抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合、顺铂和紫杉醇各一次。或者，每3周为一个治疗周期，在每个治疗周期分别给予抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合、卡铂和紫杉醇各一次。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予抗TIM-3抗体或其抗原结合片段，在每个治疗周期第1天给予抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予顺铂或卡铂，在每个治疗周期的第1天给予紫杉醇。在一些实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予抗TIM-3抗体或其抗原结合片段一次，在每个治疗周期第1天给予抗PD-1抗体或其抗原结合片段一次，在每个治疗周期第1天给予顺铂或卡铂一次，在每个治疗周期的第1天给予紫杉醇一次。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。在这些实施方案中，每3周为一个治疗周期，在每个治疗周期给予所述单一制剂和化疗药物。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期给予所述单一制剂、顺铂和紫杉醇。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期给予所述单一 制剂、卡铂和紫杉醇。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期分别给予所述单一制剂、顺铂和紫杉醇各一次。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期分别给予所述单一制剂、卡铂和紫杉醇各一次。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期的第1天给予所述单一制剂，在每个治疗周期第1天给予顺铂或卡铂，在每个治疗周期的第1天给予紫杉醇。或者，在这些实施方案中，每3周为一个治疗周期，在每个治疗周期的第1天给予所述单一制剂一次，在每个治疗周期第1天给予顺铂或卡铂一次，在每个治疗周期的第1天给予紫杉醇一次。
在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，在每个治疗周期给予75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予48-75mg/m2的顺铂，在每个治疗周期给予112-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予75mg/m2的顺铂，在每个治疗周期给予175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予30-75mg/m2的顺铂，在每个治疗周期给予67.5-150mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予60-75mg/m2的顺铂，在每个治疗周期给予135-150mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予60-75mg/m2的顺铂，在每个治疗周期给予135-150mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予48-75mg/m2的顺铂，在每个治疗周期第1天给予112-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予75mg/m2的顺铂，在每个治疗周期第1天给予175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予60-75mg/m2的顺铂，在每个治疗周期第1天给予135-150mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予60-75mg/m2的顺铂，在每个治疗周期第1天给予135-150mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予约60mg/m2或约75mg/m2的顺铂，在每个治疗周期第1天给予约135mg/m2或约150mg/m2的紫杉醇。
在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，在每个治疗周期给予75-175mg/m2、100-175 mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予3.2-5mg/(mL/min)AUC的卡铂，在每个治疗周期给予112-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期给予5mg/(mL/min)AUC的卡铂，在每个治疗周期给予175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg或约1500mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予3.2-5mg/(mL/min)AUC的卡铂，在每个治疗周期第1天给予112-175mg/m2的紫杉醇。在一些具体的实施方案中，在所述方法或用途中，每3周为一个治疗周期，在每个治疗周期的第1天给予约1200mg的抗TIM-3抗体或其抗原结合片段，在每个治疗周期的第1天给予约200mg的抗PD-1抗体或其抗原结合片段，在每个治疗周期第1天给予5mg/(mL/min)AUC的卡铂，在每个治疗周期第1天给予175mg/m2的紫杉醇。
在一些实施方案中，在每一个治疗周期中，以(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1的抗TIM-3抗体或其抗原结合片段:抗PD-1抗体或其抗原结合片段的质量比，向受试者给予抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；可选地，向受试者进一步给予化疗药物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些具体实施方案中，所述化疗药物为顺铂和紫杉醇。在另一些具体实施方案中，所述化疗药物为卡铂和紫杉醇。在一些实施方案中，在每一个治疗周期中，以(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1的抗TIM-3抗体或其抗原结合片段:抗PD-1抗体或其抗原结合片段的质量比，向受试者给予抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；可选地，向受试者进一步给予顺铂和紫杉醇。在一些实施方案中，在每一个治疗周期中，以(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1的抗TIM-3抗体或其抗原结合片段:抗PD-1抗体或其抗原结合片段的质量比，向受试者给予抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段；可选地，向受试者进一步给予卡铂和紫杉醇。
在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段以多剂量或单剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段均以多剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物以多剂量或单剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇以多剂量或单剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇均以多剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇以多剂量或单剂量给予。在一些实施方案中，在每一个治疗周期中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇均以多剂量给予。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段可以选自0.01至50mg/kg、0.1至40mg/kg、0.1至35mg/kg、0.1至30mg/kg、0.1至25mg/kg、0.1至20mg/kg、0.1至15mg/kg、0.1至10mg/kg、1至40mg/kg、1至35mg/kg、1至30mg/kg、1至25mg/kg、1至20mg/kg、1至15mg/kg、1至10mg/kg、1至3mg/kg、3至40mg/kg、3至35mg/kg、3至30mg/kg、3至25mg/kg、3至20mg/kg、3至15mg/kg、3至10mg/kg、10至40mg/kg、10至30mg/kg、10至25mg/kg、或20至25mg/kg的剂量给予受试者；或者以1-2400mg、20-1800mg、100-1800mg、300-1800mg、600-1600mg、700-1600mg、800-1600mg、900-1600mg、1000-1600mg、1100-1600mg、1200-1600mg、1300-1600mg、1400-1600mg、1500-1600mg、600-1500mg、800-1500mg、1000-1500mg、1200-1500mg、600-1200mg、800-1200mg、1200mg至1800mg、800mg、1000mg、1200mg、1600mg或1800mg的统一剂量施用于受试者。
在一些实施方案中，在所述方法或用途中，所述抗PD-1抗体或其抗原结合片段可以选自0.01至50 mg/kg、0.1至40mg/kg、0.1至35mg/kg、0.1至30mg/kg、0.1至25mg/kg、0.1至20mg/kg、0.1至15mg/kg、0.1至10mg/kg、1至30mg/kg、1至25mg/kg、1至20mg/kg、1至15mg/kg、1至10mg/kg、1至8mg/kg、1至5mg/kg、1至3mg/kg、3至30mg/kg、3至25mg/kg、3至20mg/kg、3至15mg/kg、3至10mg/kg、3至8mg/kg、或3至5mg/kg的剂量给予受试者；或者以1-1000mg、10-1000mg、10-800mg、20-800mg、40-800mg、50-700mg、50-600mg、50-500mg、60-500mg、80-500mg、100-500mg、200-500mg、100-500mg、100-400mg、50-350mg、100-300mg、50-200mg、100-200mg、100mg或200mg的统一剂量施用于受试者。
在一些实施方案中，在所述方法或用途中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、化疗药物(例如，顺铂和紫杉醇，或者卡铂和紫杉醇)的给药方案(例如，给药周期、给药剂量及剂量调整)可根据疾病的严重程度、疾病的响应、任何治疗相关的毒性、患者的年龄和健康状态进行调整。例如，可以将抗TIM-3抗体或其抗原结合片段和/或抗PD-1抗体或其抗原结合片段的一个治疗周期调整为4周、5周、6周、7周、8周、9周、10周、11周、12周、13周、14周或15周。例如，可以将顺铂、卡铂和/或紫杉醇的给药剂量调整为初始给药剂量的80％、75％或64％。例如，可以将顺铂、卡铂和/或紫杉醇的一个治疗周期调整为4周。
抗TIM-3抗体或其抗原结合片段
在一些实施方案中，本公开所述的抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:1或21所示氨基酸序列的重链CDR1(HCDR1)，SEQ ID NO:2或22所示氨基酸序列的HCDR2，SEQ ID NO:3或23所示氨基酸序列的HCDR3，SEQ ID NO:4或24所示氨基酸序列的轻链CDR1(LCDR1)，SEQ ID NO:5或25所示氨基酸序列的LCDR2，和SEQ ID NO:6或26所示氨基酸序列的LCDR3。在一些实施方案中，本公开所述的抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3。在一些实施方案中，本公开所述的抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3。抗TIM-3抗体或其抗原结合片段的CDR序列于表1中示出。
表1.抗TIM-3抗体或其抗原结合片段的CDR序列
本领域技术人员应当理解的是，除非另有规定，否则术语给定抗体或其区(例如可变区)的“CDR”或“互补决定区”应理解为涵盖通过任何一种已知方案界定的互补决定区。虽然表1已经示出了CDR序列(其中，SEQ ID NO:1-6所示的CDR区由AbM编号系统定义)，然而，在涉及用某些划分定义的具体CDR序列限定抗体时，所述抗体的范围还涵盖了转换为其他任意编号系统定义(例如本领域所公知的Kabat、Chothia、IMGT、CCG或Contact等定义中的一种或几种的结合)的CDR序列限定的抗体。例如，包含下述氨基酸序列的抗TIM-3抗体或其抗原结合片段也涵盖在本公开的抗TIM-3抗体或其抗原结合片段的范围内：SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，ARRYYGYDAMDY(SEQ ID NO:31)所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:7或27所示 氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:8或28所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包SEQ ID NO:7所示氨基酸序列的重链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包SEQ ID NO:8所示氨基酸序列的轻链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:7或27所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链可变区，和氨基酸序列与SEQ ID NO:8或28所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含SEQ ID NO:7所示氨基酸序列的重链可变区，和SEQ ID NO:8所示氨基酸序列的轻链可变区。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含SEQ ID NO:27所示氨基酸序列的重链可变区，和SEQ ID NO:28所示氨基酸序列的轻链可变区。在一些具体的实施方案中，所述抗TIM-3抗体或其抗原结合片段的重链可变区的氨基酸序列如SEQ ID NO:7所示，和轻链可变区的氨基酸序列如SEQ ID NO:8所示。在一些具体的实施方案中，所述抗TIM-3抗体或其抗原结合片段的重链可变区的氨基酸序列如SEQ ID NO:27所示，和轻链可变区的氨基酸序列如SEQ ID NO:28所示。
在一些实施方案中，本公开所述的抗TIM-3抗体或其抗原结合片段包含重链可变区和轻链可变区，其中重链可变区包含HCDR1、HCDR2和HCDR3，轻链可变区包含LCDR1、LCDR2和LCDR3，其中，HCDR1包含SEQ ID NO:1所示氨基酸序列，HCDR2包含SEQ ID NO:2所示氨基酸序列，HCDR3包含SEQ ID NO:3所示氨基酸序列，LCDR1包含SEQ ID NO:4所示氨基酸序列，LCDR2包含SEQ ID NO:5所示氨基酸序列，和LCDR3包含SEQ ID NO:6所示氨基酸序列，并且，重链可变区包含与SEQ ID NO:7具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的氨基酸序列，和轻链可变区包含与SEQ ID NO:8具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的氨基酸序列。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段还可包含免疫球蛋白的恒定区，或所述恒定区的片段、类似物、变体或衍生物。在一些实施方案中，所述重链恒定区来自人免疫球蛋白重链，例如IgG1、IgG2、IgG3和IgG4或其他类别免疫球蛋白的重链，优选为IgG4的重链。在一些实施方案中，所述轻链恒定区来自人免疫球蛋白轻链，例如人免疫球蛋白的κ轻链或λ轻链。在一些实施方案中，所述恒定区可包含任何文本所述的修饰，例如氨基酸的插入、缺失、取代或化学修饰。在一些实施方案中，所述恒定区包含改变效应功能的突变。在一些实施方案中，所述恒定区的任意氨基酸残基可用任意同种异型(allotype)的氨基酸残基取代。
在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:9或29所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:10或30所示氨基酸序列具有至少80％、81％、82％、 83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包SEQ ID NO:9所示氨基酸序列的重链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包SEQ ID NO:10所示氨基酸序列的轻链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:9或29所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链，和氨基酸序列与SEQ ID NO:10或30所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含SEQ ID NO:9所示氨基酸序列的重链，和SEQ ID NO:10所示氨基酸序列的轻链。在一些实施方案中，所述抗TIM-3抗体或其抗原结合片段包含SEQ ID NO:29所示氨基酸序列的重链，和SEQ ID NO:30所示氨基酸序列的轻链。在一些具体的实施方案中，所述抗TIM-3抗体或其抗原结合片段的重链的氨基酸序列如SEQ ID NO:9所示，和轻链的氨基酸序列如SEQ ID NO:10所示。在一些具体的实施方案中，所述抗TIM-3抗体或其抗原结合片段的重链的氨基酸序列如SEQ ID NO:29所示，和轻链的氨基酸序列如SEQ ID NO:30所示。
在一些实施方案中，本公开的抗TIM-3抗体或其抗原结合片段是公开号为WO2020041520或CN112566936的专利申请文件中记载的mAb 50B5或其抗原结合片段，或mAb 50B5的嵌合抗体或其抗原结合片段，或mAb 50B5的人源化抗体或其抗原结合片段。
在另一些实施方案中，本公开的抗TIM-3抗体或其抗原结合片段是公开号为WO2020041520或CN112566936的专利申请文件中记载的mAb 15B4或其抗原结合片段，或mAb 15B4的嵌合抗体或其抗原结合片段，或mAb 15B4的人源化抗体或其抗原结合片段。
在另一些实施方案中，本公开的抗TIM-3抗体或其抗原结合片段选自Sabatolimab、Cobolimab、Surzebiclimab、Roche的Lomvastomig(RG-7769)、恒瑞医药的SHR-1702、Agenus的Verzistobart(INCAGN-2390)、药明生物的BC-3402、维立志博的LBL-003、健信生物的LNL-005、或BMS的BMS-986258。
抗PD-1抗体或其抗原结合片段
在一些实施方案中，本公开所述的抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3。抗PD-1抗体或其抗原结合片段CDR序列于表2中示出。
表2.抗PD-1抗体或其抗原结合片段的CDR序列
本领域技术人员应当理解的是，除非另有规定，否则术语给定抗体或其区(例如可变区)的“CDR”或“互补决定区”应理解为涵盖通过任何一种已知方案界定的互补决定区。虽然表2中已经示出了CDR区，然而，在涉及用某些划分定义的具体CDR序列限定抗体时，所述抗体的范围还涵盖了转换为其他任意编号系统定义(例如本领域所公知的AbM、Kabat、Chothia、IMGT、CCG或Contact等定义中的一种或几种的结合)的CDR序列限定的抗体。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:17所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链可变区。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:18所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链可变区。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包SEQ ID NO:17所示氨基酸序列的重链可变区。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包SEQ ID NO:18所示氨基酸序列的轻链可变区。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:17所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链可变区，和氨基酸序列与SEQ ID NO:18所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链可变区。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含SEQ ID NO:17所示氨基酸序列的重链可变区，和SEQ ID NO:18所示氨基酸序列的轻链可变区。在一些具体的实施方案中，所述抗PD-1抗体或其抗原结合片段的重链可变区的氨基酸序列如SEQ ID NO:17所示，和轻链可变区的氨基酸序列如SEQ ID NO:18所示。
在一些实施方案中，本公开所述的抗PD-1抗体或其抗原结合片段包含重链可变区和轻链可变区，其中重链可变区包含HCDR1、HCDR2和HCDR3，轻链可变区包含LCDR1、LCDR2和LCDR3，其中，HCDR1包含SEQ ID NO:11所示氨基酸序列，HCDR2包含SEQ ID NO:12所示氨基酸序列，HCDR3包含SEQ ID NO:13所示氨基酸序列，LCDR1包含SEQ ID NO:14所示氨基酸序列，LCDR2包含SEQ ID NO:15所示氨基酸序列，和LCDR3包含SEQ ID NO:16所示氨基酸序列，并且，重链可变区包含与SEQ ID NO:17具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的氨基酸序列，和轻链可变区包含与SEQ ID NO:18具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的氨基酸序列。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段还可包含免疫球蛋白的恒定区，或所述恒定区的片段、类似物、变体或衍生物。在一些实施方案中，所述重链恒定区来自人免疫球蛋白重链，例如IgG1、IgG2、IgG3和IgG4或其他类别免疫球蛋白的重链，优选为IgG1的重链。在一些实施方案中，所述轻链恒 定区来自人免疫球蛋白轻链，例如人免疫球蛋白的κ轻链或λ轻链。在一些实施方案中，所述恒定区可包含任何文本所述的修饰，例如氨基酸的插入、缺失、取代或化学修饰。在一些实施方案中，所述恒定区包含改变效应功能的突变。在一些实施方案中，所述恒定区的任意氨基酸残基可用任意同种异型(allotype)的氨基酸残基取代。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:19所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:20所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包SEQ ID NO:19所示氨基酸序列的重链。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包SEQ ID NO:20所示氨基酸序列的轻链。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含氨基酸序列与SEQ ID NO:19所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的重链，和氨基酸序列与SEQ ID NO:20所示氨基酸序列具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％或100％同一性的轻链。在一些实施方案中，所述抗PD-1抗体或其抗原结合片段包含SEQ ID NO:19所示氨基酸序列的重链，和SEQ ID NO:20所示氨基酸序列的轻链。在一些具体的实施方案中，所述抗PD-1抗体或其抗原结合片段的重链氨基酸序列如SEQ ID NO:19所示，和轻链氨基酸序列如SEQ ID NO:20所示。
在另一些实施方案中，本公开的抗PD-1抗体或其抗原结合片段选自纳武利尤单抗(Nivolumab)、帕博利珠单抗(Pembrolizumab)、特瑞普利单抗(Toripalimab)、信迪利单抗(Sintilimab)、卡瑞利珠单抗(Camrelizumab)、替雷利珠单抗(Tislelizumab)、赛帕利单抗(Zimberelimab)、巴替利单抗(Balstilimab)、杰诺单抗(geptanolimab)、丽珠医药的Lipustobart(LZM-009)、西米普利单抗(Cemiplimab)、斯鲁利单抗(Serplulimab)、Prolgolimab、普特利单抗Pucotenlimab(HX008)、Nofazinlimab、Finotonlimab、Dostarlimab、Cetrelimab、齐鲁制药的QL1604、Spartalizumab、Retifanlimab、Sasanlimab、山东新时代药业的Rulonilimab(F520)、或尚健生物的Enlonstobart(SG001)。
含抗体或其抗原结合片段的药物组合物
在一些实施方案中，抗TIM-3抗体或其抗原结合片段和/或抗PD-1抗体或其抗原结合片段配制为用于胃肠外途径施用的制剂。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段和/或抗PD-1抗体或其抗原结合片段配制为用于静脉内、肌肉内、皮下或其它胃肠外途径施用的制剂，例如用于注射或输注。在一些具体的实施方案中，用于静脉内、肌肉内或皮下施用。在一些具体的实施方案中，用于静脉注射或输注。
抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段可以配制成适合的剂型，包括但不限于，片剂、含片、丸剂、胶囊剂(例如硬胶囊、软胶囊、肠溶胶囊、微囊剂)、酏剂、颗粒剂、糖浆剂、注射剂(即适合注射的制剂，例如适合肌肉内、静脉内、腹腔内、皮下注射的制剂)、颗粒剂、乳剂、悬浮 液、溶液、分散剂和用于口服或非口服给药的缓释制剂的剂型。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段可以配制成注射剂。在一些具体的实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段可以配制成适合静脉注射的制剂。
在一些实施方案中，抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。在一些实施方案中，抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段与一种或多种药学上可接受的载体配制在一起以制成合适的药物组合物。
在一些实施方案中，抗TIM-3抗体或其抗原结合片段与抗PD-1抗体或其抗原结合片段分开配制(即，各自呈药物组合物的形式)。在一些实施方案中，抗TIM-3抗体或其抗原结合片段与一种或多种药学上可接受的载体配制在一起以制成合适的药物组合物。在一些实施方案中，抗PD-1抗体或其抗原结合片段与一种或多种药学上可接受的载体配制在一起以制成合适的药物组合物。
药学上可接受的载体包括，例如，赋形剂、稀释剂、包封材料、填充剂、缓冲剂或其他试剂。
在一些实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物的单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg的抗TIM-3抗体或其抗原结合片段，例如约60mg、约120mg、约160mg、约180mg、约200mg、约240mg、约280mg、约300mg、约320mg、约360mg、约400mg、约420mg、约440mg、约480mg、约520mg、约540mg、约560mg、约600mg、约640mg、约660mg、约680mg、约720mg、约760mg、约780mg、约800mg、约840mg、约880mg、约900mg、约920mg、约960mg、约1000mg、约1020mg、约1040mg、约1080mg、约1120mg、约1140mg、约1160mg、约1200mg、约1240mg、约1260mg、约1280mg、约1320mg、约1360mg、约1380mg、约1400mg、约1440mg、约1480mg、约1500mg、约1520mg、约1560mg、约1600mg、约1620mg、约1640mg、约1680mg、约1720mg、约1740mg、约1760mg和/或约1800mg、或上述任意值形成的范围的抗TIM-3抗体或其抗原结合片段。
在一些实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物的单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg的抗PD-1抗体或其抗原结合片段，例如约10mg、约20mg、约30mg、约40mg、约50mg、约60mg、约70mg、约80mg、约90mg、约100mg、约110mg、约120mg、约130mg、约140mg、约150mg、约160mg、约170mg、约180mg、约190mg、约200mg、约210mg、约220mg、约230mg、约240mg、约250mg、约260mg、约270mg、约280mg、约290mg、约300mg、约310mg、约320mg、约330mg、约340mg、约350mg、约360mg、约370mg、约380mg、约390mg、约400mg、约410mg、约420mg、约430mg、约440mg、约450mg、约460mg、约470mg、约480mg、约490mg和/或约500mg、或上述任意值形成的范围的抗PD-1抗体或其抗原结合片段。
在一个具体实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为水溶性注射液。在一个具体实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为水溶性注射液。在一个具体实施方案中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为水溶性注射液。所述水溶性注射液包括但不限于未经冻干的水溶性制剂或冻干粉重构的水溶性制剂。
在另一些实施方案中，含抗TIM-3抗体或其抗原结合片段的药物组合物为冻干制剂。在另一些实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。在一个具体实施方案中，含抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合物为冻干制剂。所述冻干制剂是指水溶液经历冻干过程制备的制剂，在该过程中物质首先被冷冻，然后先通过升华降低溶剂数量(初级干燥过程)，然后通过脱附作用降低溶剂数量(二级干燥过程)，直到溶剂数量为不再支持生物学活性或化学反应的值。本公开的冻干制剂还可以通过本领域已知的其它方法干燥，如喷雾干燥和鼓泡干燥(bubble drying)。
在一些实施方案中，含抗PD-1抗体或其抗原结合片段的药物组合物中抗PD-1抗体或其抗原结合片段的浓度为0.1-50mg/mL、0.5-30mg/mL、0.8-20mg/mL、1-15mg/mL、1-10mg/mL、1-5mg/mL、2-20mg/mL、2-15mg/mL、2-10mg/mL、或2-5mg/mL。在一些具体的实施方案中，抗PD-1抗体或其抗原结合片段的浓度为约0.8mg/mL、约1mg/mL、约2mg/mL、约3mg/mL、约4mg/mL、约5mg/mL、约6mg/mL、约7mg/mL、约8mg/mL、约9mg/mL、约10mg/mL、约15mg/mL、或约20mg/mL。在一些实施方案中，抗PD-1抗体或其抗原结合片段的浓度为约1mg/mL。在一些实施方案中，抗PD-1抗体或其抗原结合片段的浓度为约2mg/mL。在一些实施方案中，抗PD-1抗体或其抗原结合片段的浓度为约5mg/mL。在一些实 施方案中，抗PD-1抗体或其抗原结合片段的浓度为约10mg/mL。
在一些实施方案中，所述抗PD-1抗体或其抗原结合片段呈药物组合物形式，其包含抗PD-1抗体或其抗原结合片段、缓冲剂、等渗调节剂/稳定剂、和表面活性剂。在一个具体实施方案中，所述抗PD-1抗体或其抗原结合片段呈液体制剂形式(例如注射液)，其包含抗PD-1抗体或其抗原结合片段、三水合乙酸钠、冰醋酸、山梨醇和聚山梨酯80。
化疗药物
在本公开一些实施方案中，所述化疗药物包括但不限于铂类抗肿瘤药物(包括但不限于奥沙利铂、顺铂、卡铂、奈达铂、双环铂、米铂、洛铂、吡铂(picoplatin)、乐铂(Lobaplatin)、四硝酸三铂、菲铂、沙铂)、喜树碱类抗肿瘤药物(包括但不限于喜树碱、羟基喜树碱、氨基喜树碱、伊立替康、拓扑替康、依喜替康、鲁比替康、勒托替康(lurtotecan)、吉马替康、karenitecin、7-乙基喜树碱)、紫杉烷类抗肿瘤药物(包括但不限于紫杉醇和多西他赛)、氮芥类抗肿瘤药物(包括但不限于环磷酰胺、异环磷酰胺、苯丁酸氮芥、卡氮芥、美法仑、苯达莫司汀)、抗代谢类抗肿瘤药物(包括但不限于氟尿嘧啶类抗肿瘤药物(包括但不限于卡莫氟、5-氟尿嘧啶、替加氟、卡培他滨、替吉奥、双呋氟尿嘧啶、去氧氟尿苷、三氟尿苷)、胞嘧啶类抗肿瘤药物(包括但不限于阿糖胞苷、吉西他滨、阿扎胞苷、安西他滨)、嘌呤类抗肿瘤药物(包括但不限于巯嘌呤、氟达拉滨)、抗叶酸类抗肿瘤药物(包括但不限于甲氨蝶呤、培美曲塞))、蒽环类抗肿瘤药物(包括但不限于多柔比星、表柔比星、吡柔比星、氨柔比星、阿柔比星、伊达比星、柔红霉素、米托蒽醌、伊达柔比星、戊柔比星、佐柔比星、匹杉琼、脂质体阿霉素)、长春碱类抗肿瘤药物(包括但不限于长春碱、长春新碱、长春地辛、长春富宁(vinflunine)和长春瑞滨)、鬼臼生物碱类抗肿瘤药物(包括但不限于依托泊苷、替尼泊苷)、激素类抗肿瘤药物(包括但不限于泼尼松、泼尼松龙、地塞米松、甲泼尼龙琥珀酸钠)、甲基苄肼、六甲嘧胺、达卡巴嗪、丝裂霉素、放线菌素D(更生霉素)、博来霉素、平阳霉素、替莫唑胺、氨烯咪胺、培洛霉素、艾日布林、普那布林(plinabulin)、Sapacitabine、曲奥舒凡(treosulfan)、153Sm-EDTMP、和encequidar中的一种或多种。
在一些实施方案中，所述化疗药物选自铂类抗肿瘤药物、紫杉烷类抗肿瘤药物、以及抗代谢类抗肿瘤药物中的一种或多种。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物。在一些实施方案中，所述化疗药物为铂类抗肿瘤药物和紫杉烷类抗肿瘤药物。
进一步地，所述铂类抗肿瘤药物选自顺铂、卡铂、奈达铂、双环铂、吡铂、奥沙利铂、米铂、洛铂、乐铂、四硝酸三铂、菲铂和沙铂中的一种或多种，优选为卡铂和/或顺铂，更优选为顺铂。
在一些实施方案中，所述紫杉烷类抗肿瘤药物包括各种结构上具有从短叶红豆杉(Taxusbrevifolia)中所分离的紫杉烷骨架的成分或其半合成产物，或具有紫杉烷骨架的纯合成产物。具体而言，包括紫杉醇、卡巴他赛、多西他赛等，优选为紫杉醇。其中紫杉醇包括但不限于紫杉醇注射液、紫杉醇冻干粉、紫杉醇脂质体和白蛋白结合型紫杉醇等。
在一些具体的实施方案中，所述化疗药物为顺铂和紫杉醇。在一些具体的实施方案中，所述化疗药物为卡铂和紫杉醇。
在一些实施方案中，所述化疗药物按照已知的给药方案(包括给药周期、给药剂量及剂量调整、给药途径)给药。
含化疗药物的药物组合物
在本公开的一些实施方案中，含顺铂的药物组合物的单位剂量为2.5mg、5mg、10mg、20mg、25mg、30mg、50mg和/或100mg的顺铂。在一些实施方案中，含顺铂的药物组合物的单位剂量为10mg、20mg、30mg、50mg和/或100mg的顺铂。
在本公开的一些实施方案中，含卡铂的药物组合物的单位剂量为50mg、100mg、150mg、250mg和/或450mg。
在本公开的一些实施方案中，含紫杉醇的药物组合物的单位剂量为30mg、60mg、100mg和/或150mg的紫杉醇。
在一些实施方案中，含顺铂的药物组合物为适合注射的制剂。在一些实施方案中，含顺铂的药物组合物为液体制剂。在一些实施方案中，含顺铂的药物组合物为适合注射的液体制剂。在一些实施方案中，含顺铂的药物组合物为适合静脉注射的液体制剂。在一些实施方案中，含顺铂的药物组合物为固体制剂。在 一些实施方案中，含顺铂的药物组合物为冻干制剂。在一些具体实施方案中，含顺铂的药物组合物为粉针制剂。合适的制剂可使用本领域公知的药学上可接受的载体通过常规方法制得。在一个特定实施方案中，适合注射的含顺铂的液体制剂的药学上可接受的载体包括聚乙二醇400和氯化钠。
在一些实施方案中，含卡铂的药物组合物为适合注射的制剂。在一些实施方案中，含卡铂的药物组合物为液体制剂。在一些实施方案中，含卡铂的药物组合物为适合注射的液体制剂。在一些实施方案中，含卡铂的药物组合物为适合静脉注射的液体制剂。在一些实施方案中，含卡铂的药物组合物为固体制剂。在一些实施方案中，含卡铂的药物组合物为冻干制剂。在一些具体实施方案中，含卡铂的药物组合物为粉针制剂。合适的制剂可使用本领域公知的药学上可接受的载体通过常规方法制得。在一个特定实施方案中，适合注射的含卡铂的液体制剂的药学上可接受的载体包括注射用水。在一个特定实施方案中，适合注射的含卡铂的固体制剂的药学上可接受的载体包括甘露醇。
在一些实施方案中，含紫杉醇的药物组合物为适合注射的制剂。在一些实施方案中，含紫杉醇的药物组合物为液体制剂。在一些实施方案中，含紫杉醇的药物组合物为适合注射的液体制剂。在一些实施方案中，含紫杉醇的药物组合物为适合静脉注射的液体制剂。在一些实施方案中，含紫杉醇的药物组合物为固体制剂。在一些实施方案中，含紫杉醇的药物组合物为冻干制剂。在一些具体实施方案中，含紫杉醇的药物组合物为粉针制剂。合适的制剂可使用本领域公知的药学上可接受的载体通过常规方法制得。在一个特定实施方案中，适合注射的含紫杉醇的液体制剂的药学上可接受的载体包括聚氧乙烯蓖麻油和无水乙醇。
施用方式
下述内容并非限制本公开的药物组合的施用方式。
本公开的药物组合中的各组分可以各自独立地、或者其中的部分或全部共同以适合的各种途径施用，包括但不限于肠胃外(例如，通过静脉内、肌内、局部或皮下途径)施用。在一些实施方案中，本公开的药物组合的各组分可以各自独立地、或者其中的部分或全部共同注射施用，例如静脉注射或皮下注射。
本公开的药物组合中的组分可以各自独立地、或者其中的部分或全部共同配制成适合的剂型，包括但不限于，片剂、含片、丸剂、胶囊剂(例如硬胶囊、软胶囊、肠溶胶囊、微囊剂)、酏剂、颗粒剂、糖浆剂、注射剂(即适合注射的制剂，例如适合肌肉内、静脉内、腹腔内、皮下注射的制剂)、颗粒剂、乳剂、悬浮液、溶液、分散剂和用于口服或非口服给药的缓释制剂的剂型。在一些实施方案中，本公开的药物组合的各组分可以各自独立地、或者其中的部分或全部共同配制成注射剂。
本公开的药物组合还可以包含另外的治疗剂。在一个实施方案中，所述另外的治疗剂可以是本领域已知的肿瘤治疗剂。
肿瘤
在某些方面，本公开所述肿瘤为恶性肿瘤(即癌症)；所述恶性肿瘤是指由异常细胞生长引起的任何恶性和/或侵袭性生长。
在一些实施方案中，所述肿瘤是实体瘤。在一些实施方案中，所述肿瘤是初治的、不可切除的、难治性的、晚期的、复发性的和/或转移性的实体瘤。在一些实施方案中，所述肿瘤是不可切除的实体瘤。在一些实施方案中，所述肿瘤为晚期的实体瘤。在一些实施方案中，所述肿瘤是局部晚期的实体瘤。在一些实施方案中，所述肿瘤为复发性和/或转移性的实体瘤。一些实施方案中，所述肿瘤为局部晚期、复发性或转移性的实体瘤。一些实施方案中，所述肿瘤为不可切除、复发性或转移性的实体瘤。
在一些实施方案中，所述肿瘤为头颈癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的头颈癌。在一些实施方案中，所述肿瘤是初治的、不可切除的、难治性的、晚期的、复发性的和/或转移性的头颈癌。在一些实施方案中，所述肿瘤是不可切除的头颈癌。在一些实施方案中，所述肿瘤为晚期的头颈癌。在一些实施方案中，所述肿瘤是局部晚期的头颈癌。在一些实施方案中，所述肿瘤为复发性和/或转移性的头颈癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的、不可切除、复发性或转移性的头颈癌。
本公开所述的头颈癌是一类癌症，其主要起始于唇部、口腔、唾液腺、咽部、喉部、鼻腔和鼻旁窦，包括但不限于外鼻-鼻腔肿瘤、鼻窦肿瘤、唇及口腔肿瘤、口咽肿瘤、下咽肿瘤、喉肿瘤、颈段气管、食管肿瘤、甲状腺肿瘤、涎腺肿瘤、颈部淋巴结转移癌、皮肤及附属器肿瘤。在一些实施方案中，所述头颈癌包括但不限于口腔肿瘤、口咽肿瘤、下咽肿瘤和喉肿瘤。在一些实施方案中，所述头颈癌包括但不限于鼻 腔肿瘤和鼻窦肿瘤。
本公开所述的头颈癌涵盖鳞状细胞癌(简称鳞癌)、基底细胞癌、腺样囊性癌、乳头状癌、滤泡状癌、髓样癌、未分化癌等。在一些实施方案中，所述头颈癌为头颈鳞状细胞癌(简称头颈鳞癌)。
在一些实施方案中，所述肿瘤是以唇部、口腔、唾液腺、咽部、喉部、鼻腔和鼻旁窦作为原发部位的转移性头颈鳞癌。在一些实施方案中，所述肿瘤是以口腔、口咽、下咽和喉部作为原发部位的转移性头颈鳞癌。在一些实施方案中，所述肿瘤是以鼻腔和鼻窦作为原发部位的转移性头颈鳞癌。
在一些实施方案中，所述头颈癌不包括鼻咽癌。在一些实施方案中，所述头颈鳞癌不包括鼻咽癌。
一些实施方案中，所述肿瘤为无局部根治性治疗指征的头颈鳞癌。在一些实施方案中，所述肿瘤是初治的、不可切除的、难治性的、晚期的、复发性的和/或转移性的头颈鳞癌。在一些实施方案中，所述肿瘤为不可切除的头颈鳞癌。在一些实施方案中，所述肿瘤为晚期的头颈鳞癌。在一些实施方案中，所述肿瘤是局部晚期的头颈鳞癌。在一些实施方案中，所述肿瘤为复发性和/或转移性的头颈鳞癌。一些实施方案中，所述肿瘤为局部晚期、复发性或转移性的头颈鳞癌。一些实施方案中，所述肿瘤为不可切除、复发性或转移性的头颈鳞癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的、复发性或转移性的头颈鳞癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞癌。一些实施方案中，所述肿瘤为无局部根治性治疗指征的、不可切除、复发性或转移性的头颈鳞癌。
在一些实施方案中，所述头颈鳞癌的主体先前未治疗过头颈鳞癌(例如，缺乏有效的治疗方案)。在一些实施方案中，所述头颈鳞癌的主体既往未接受过放射疗法、化学疗法和/或免疫疗法以治疗头颈鳞癌。在一些实施方案中，所述头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。
在一些实施方案中，所述无局部根治性治疗指征的头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述初治的、不可切除的、难治性的、晚期的、复发性的和/或转移性的头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述不可切除的头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述晚期头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述局部晚期头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述复发性和/或转移性头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、复发性或转移性头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、局部晚期、复发性或转移性头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、不可切除、复发性或转移性头颈鳞癌的主体既往未接受过系统治疗以治疗头颈鳞癌。
在一些实施方案中，所述无局部根治性治疗指征的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述初治的、不可切除的、难治性的、晚期的、复发性的和/或转移性的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述不可切除的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述晚期的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述局部晚期的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述复发性和/或转移性的头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、复发性或转移性头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、局部晚期、复发性或转移性头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、不可切除、复发性或转移性头颈鳞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗头颈鳞癌。
在一些实施方案中，所述头颈鳞癌的主体先前已经用一种或多种不同的抗肿瘤治疗方法治疗过头颈鳞 癌。在一些方案中，所述头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌。在一些实施方案中，所述头颈鳞癌的主体先前接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗头颈鳞癌。在一些具体实施方式中，所述头颈鳞癌的主体先前未接受过系统化疗，但是接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌。在一些具体实施方式中，所述头颈鳞癌的主体先前未接受过系统化疗，但是接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗头颈鳞癌。在一些具体实施方式中，所述头颈鳞癌的主体经手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗后，获完全缓解或部分缓解后再次出现疾病进展。在一些具体实施方式中，所述头颈鳞癌的主体经手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗后癌症发生转移。在一些具体实施方式中，所述头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)出现疾病进展。在一些具体实施方式中，所述头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)癌症发生转移。
在一些实施方案中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体先前已经用一种或多种不同的抗肿瘤治疗方法治疗过头颈鳞癌。在一些实施方案中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌。在一些具体实施方式中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体先前未接受过系统化疗，但是接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌。在一些具体实施方式中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体经手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗后，获完全缓解或部分缓解后再次出现疾病进展。在一些具体实施方式中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体经手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗后癌症发生转移。在一些具体实施方式中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)出现疾病进展。在一些具体实施方式中，所述无局部根治性治疗指征的、局部晚期、复发性和/或转移性的头颈鳞癌的主体先前接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗头颈鳞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)癌症发生转移。
在一些实施方案中，所述肿瘤为食管癌。在一些实施方案中，所述肿瘤是初治的、不可切除的、难治性的、复发性的、转移性的和/或晚期的食管癌。在一些实施方案中，所述肿瘤为初治的食管癌。在一些实施方案中，所述肿瘤为不可切除的食管癌。在一些实施方案中，所述肿瘤为晚期的食管癌。一些实施方案中，所述肿瘤为局部晚期的食管癌。在一些实施方案中，所述肿瘤为复发性和/或转移性的食管癌。在一些实施方案中，所述肿瘤为局部晚期、复发性或转移性的食管癌。在一些实施方案中，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管癌。
在一些实施方案中，所述食管癌为食管鳞状细胞癌(即食管鳞癌)、食管腺癌、横跨食管胃交界部的鳞状细胞癌、或食管胃交界部腺癌。在一些实施方案中，所述食管癌为食管鳞状细胞癌或食管腺癌。在一些具体的方案中，所述食管癌是初治的食管鳞状细胞癌。在一些实施方案中，所述肿瘤为不可切除的食管鳞状细胞癌。在一些实施方案中，所述肿瘤为晚期的食管鳞状细胞癌。一些实施方案中，所述肿瘤为局部晚期的食管鳞状细胞癌。在一些实施方案中，所述肿瘤为复发性和/或转移性的食管鳞状细胞癌。在一些实施方案中，所述肿瘤为局部晚期、复发性或转移性的食管鳞状细胞癌。在一些实施方案中，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌。
在一些实施方案中，所述食管癌的主体先前未治疗过食管癌(例如，缺乏有效的治疗方案)。在一些实施方案中，所述食管癌的主体既往未接受过放射疗法、化学疗法和/或免疫疗法以治疗食管癌。在一些实施方案中，所述食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。
在一些实施方案中，所述初治的食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述不可切除的食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述晚期食 管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述局部晚期食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述复发性和/或转移性食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述局部晚期、复发性或转移性食管癌的主体既往未接受过系统治疗以治疗食管癌。在一些实施方案中，所述不可切除、局部晚期、复发性或转移性食管癌的主体既往未接受过系统治疗以治疗食管癌。
在一些实施方案中，所述初治的食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述不可切除的食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述晚期的食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述局部晚期的食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述复发性和/或转移性的食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述局部晚期、复发性或转移性食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。在一些实施方案中，所述不可切除、局部晚期、复发性或转移性食管癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管癌。
在一些实施方案中，所述食管鳞状细胞癌的主体先前未治疗过食管鳞状细胞癌(例如，缺乏有效的治疗方案)。在一些实施方案中，所述食管鳞状细胞癌的主体既往未接受过放射疗法、化学疗法和/或免疫疗法以治疗食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。
在一些实施方案中，所述初治的食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述不可切除的食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述晚期食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述局部晚期食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述复发性和/或转移性食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述局部晚期、复发性或转移性食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。在一些实施方案中，所述不可切除、局部晚期、复发性或转移性食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
在一些实施方案中，所述初治的食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述不可切除的食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述晚期的食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述局部晚期的食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述复发性和/或转移性的食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述局部晚期、复发性或转移性食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。在一些实施方案中，所述不可切除、局部晚期、复发性或转移性食管鳞状细胞癌的主体既往未接受过免疫检查点(例如，PD-1、PD-L1、CTLA-4或TIM-3)抑制剂以治疗食管鳞状细胞癌。
在一些实施方案中，所述食管癌的主体先前已经用一种或多种不同的抗肿瘤治疗方法治疗过食管癌。在一些方案中，所述食管癌的主体既往接受过手术治疗、放射治疗、诱导化疗、同期的化疗和/或辅助化疗以治疗食管癌。在一些实施方案中，所述食管癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管癌。
在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的食管癌。在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的食管癌。在一些 具体的实施方案中，所述食管癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的局部晚期食管癌。在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的局部晚期食管癌。在一些具体的实施方案中，所述局部晚期食管癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的复发性和/或转移性食管癌。在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的复发性和/或转移性食管癌。在一些具体的实施方案中，所述复发性和/或转移性食管癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的不可切除、局部晚期、复发性或转移性食管癌。在一些实施方案中，所述食管癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的不可切除、局部晚期、复发性或转移性食管癌。在一些具体的实施方案中，所述不可切除、局部晚期、复发性或转移性食管癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管鳞状细胞癌的主体先前已经用一种或多种不同的抗肿瘤治疗方法治疗过食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管鳞状细胞癌。
在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的食管鳞状细胞癌。在一些具体的实施方案中，所述食管鳞状细胞癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管鳞状细胞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的局部晚期食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的局部晚期食管鳞状细胞癌。在一些具体的实施方案中，所述局部晚期食管鳞状细胞癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管鳞状细胞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的复发性和/或转移性食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的复发性和/或转移性食管鳞状细胞癌。在一些具体的实施方案中，所述复发性和/或转移性食管鳞状细胞癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管鳞状细胞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗失败的不可切除、局部晚期、复发性或转移性食管鳞状细胞癌。在一些实施方案中，所述食管鳞状细胞癌为新辅助治疗、辅助治疗或根治性同步放化疗治疗后复发的不可切除、局部晚期、复发性或转移性食管鳞状细胞癌。在一些具体的实施方案中，所述不可切除、局部晚期、复发性或转移性食管鳞状细胞癌的主体既往接受过新辅助治疗、辅助治疗或根治性同步放化疗以治疗食管鳞状细胞癌，且在停止治疗6个月后(例如6、7、8、9或10个月)疾病复发。
本公开还提供了以下一些具体的实施方案，但本公开的保护范围不限于此：
实施方案1.一种药物组合，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，其中，所述抗TIM-3抗体或其抗原结合片段包含：
SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或
SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3。
实施方案2.根据实施方案1所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段包含：
氨基酸序列与SEQ ID NO:7所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:8所示氨基酸序列具有至少95％同一性的轻链可变区；或
氨基酸序列与SEQ ID NO:27所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:28所示氨基酸序列具有至少95％同一性的轻链可变区。
实施方案3.根据实施方案1或2所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段包含：
氨基酸序列与SEQ ID NO:9所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:10所示氨基酸序列具有至少95％同一性的轻链；或
氨基酸序列与SEQ ID NO:29所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:30所示氨基酸序列具有至少95％同一性的轻链。
实施方案4.根据实施方案1-3中任一项所述的药物组合，其中，所述抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3。
实施方案5.根据实施方案1-4中任一项所述的药物组合，其中，所述抗PD-1抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:17所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:18所示氨基酸序列具有至少95％同一性的轻链可变区。
实施方案6.根据实施方案1-5中任一项所述的药物组合，其中，所述抗PD-1抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:19所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:20所示氨基酸序列具有至少95％同一性的轻链。
实施方案7.根据实施方案1-6中任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于胃肠外施用的制剂，优选地，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于静脉内、肌肉内或皮下施用的制剂。
实施方案8.根据实施方案1-7中任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。
实施方案9.根据实施方案1-8中任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分开配制。
实施方案10.根据实施方案1-9中任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段的单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg；优选地，所述抗TIM-3抗体或其抗原结合片段的单位剂量为240mg、300mg、360mg和/或600mg。
实施方案11.根据实施方案1-10中任一项所述的药物组合，其中，所述抗PD-1抗体或其抗原结合片段的单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg；优选地，所述抗PD-1抗体或其抗原结合片段的单位剂量为100mg和/或200mg。
实施方案12.根据实施方案1-11中任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的质量比为(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1。
实施方案13.根据实施方案1-12中任一项所述的药物组合，其中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，优选1200mg或1500mg的抗TIM-3抗体或其抗原结合片段；和/或
10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，优选200mg的抗PD-1抗体或其抗原结合片段。
实施方案14.根据实施方案1-13中任一项所述的药物组合，所述药物组合还包括化疗药物。
实施方案15.根据实施方案14所述的药物组合，其中，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物；
可选地，所述铂类抗肿瘤药物选自顺铂、卡铂、奈达铂、双环铂、吡铂、奥沙利铂、米铂、洛铂、乐铂、四硝酸三铂、菲铂和沙铂中的一种或多种；
可选地，所述紫杉烷类抗肿瘤药物选自紫杉醇、卡巴他赛和多西他赛中的一种或多种。
实施方案16.根据实施方案14所述的药物组合，其中，所述化疗药物为顺铂和紫杉醇，或者，所述化疗药物为卡铂和紫杉醇。
实施方案17.根据实施方案14-16中任一项所述的药物组合，其中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，优选1200mg或1500mg的抗TIM-3抗体或其抗原结合片段；和/或
10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，优选200mg的抗PD-1抗体或其抗原结合片段。
实施方案18.根据实施方案14-16中任一项所述的药物组合，其中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的顺铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇；或者包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段，10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段，2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的卡铂，和75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的紫杉醇。
实施方案19.实施方案1-13中任一项所述的药物组合在制备用于治疗受试者中肿瘤的药物中的用途。
实施方案20.根据实施方案19所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，可同时、先后和/或交替给药。
实施方案21.根据实施方案19或20所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗TIM-3抗体或其抗原结合片段每3周施用一次；可选地，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用，优选地，所述抗TIM-3抗体或其抗原结合片段每次以1200mg的剂量施用。
实施方案22.根据实施方案19-21中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗PD-1抗体或其抗原结合片段每3周施用一次；可选地，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用，优选地，所述抗PD-1抗体或其抗原结合片段每次以200mg的剂量施用。
实施方案23.实施方案14-18中任一项所述的药物组合在制备用于治疗受试者中肿瘤的药物中的用途。
实施方案24.根据实施方案23所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇，可同时、先后和/或交替给药；或者所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇，可同时、先后和/或交替给药。
实施方案25.根据实施方案23或24所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗TIM-3抗体或其抗原结合片段每3周施用一次；可选地，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用，优选地，所述抗TIM-3抗体或其抗原结合片段每次以1200mg的剂量施用。
实施方案26.根据实施方案23-25中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗PD-1抗体或其抗原结合片段每3周施用一次；可选地，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用，优选地，所述抗PD-1抗体或其抗原结合片段每次以200mg的剂量施用。
实施方案27.根据实施方案23-26中任一项所述的用途，其中，所述顺铂每1周、每2周、每3周、或每4周施用一次，优选地，所述顺铂每3周施用一次；可选地，所述顺铂每次以30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的剂量施用，优选地，所述顺铂每次以60-75mg/m2的剂量施用；或者 所述卡铂每1周、每2周、每3周、或每4周施用一次，优选地，所述卡铂每3周施用一次；可选地，所述卡铂每次以2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的剂量施用，优选地，所述卡铂每次以3.2-5mg/(mL/min)AUC的剂量施用。
实施方案28.根据实施方案23-27中任一项所述的用途，其中，所述紫杉醇每1周、每2周、每3周、或每4周施用一次，优选地，所述紫杉醇每3周施用一次；可选地，所述紫杉醇每次以75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的剂量施用，优选地，所述紫杉醇每次以135-175mg/m2的剂量施用。
实施方案29.根据实施方案19-28中任一项所述的用途，其中，所述肿瘤为头颈癌；优选地，所述肿瘤为头颈鳞状细胞癌；优选地，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞状细胞癌。
实施方案30.根据实施方案29所述的用途，其中，所述头颈鳞状细胞癌的主体既往未接受过系统治疗以治疗头颈鳞状细胞癌。
实施方案31.根据实施方案19-28中任一项所述的用途，其中，所述肿瘤为食管癌；优选地，所述肿瘤为食管鳞状细胞癌；优选地，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌。
实施方案32.根据实施方案31所述的用途，其中，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
实施方案33.一种在受试者中治疗肿瘤的方法，其中，所述方法包括向受试者给予实施方案1-18中任一项所述的药物组合。
实施方案34.根据实施方案33所述的方法，其中，所述方法包括在第一治疗阶段向受试者给予实施方案14-18中任一项所述的药物组合，并且在第二治疗阶段向受试者给予实施方案1-13中任一项所述的药物组合。
实施方案35.根据实施方案33或34所述的方法，其中，所述第一治疗阶段包括1-14个治疗周期、2-12个治疗周期或2-10个治疗周期，优选2-8个治疗周期，更优选4-6个治疗周期。
实施方案36.根据实施方案35所述的方法，其中，每1周、每2周、每3周、或每4周为一个治疗周期，优选地，每3周为一个治疗周期。
实施方案37.根据实施方案33-36中任一项所述的方法，其中，所述肿瘤为头颈癌；优选地，所述肿瘤为头颈鳞状细胞癌；优选地，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞状细胞癌。
实施方案38.根据实施方案37所述的用途，其中，所述头颈鳞状细胞癌的主体既往未接受过系统治疗以治疗头颈鳞状细胞癌。
实施方案39.根据实施方案33-36中任一项所述的用途，其中，所述肿瘤为食管癌；优选地，所述肿瘤为食管鳞状细胞癌；优选地，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌。
实施方案40.根据实施方案39所述的用途，其中，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
实施方案41.一种用于治疗肿瘤的试剂盒，其包含实施方案1-18中任一项所述的药物组合。
实施方案42.一种联用药物组合，其包括：
a)实施方案14-18中任一项所述的药物组合，其被制备为适合在第一治疗阶段施用；和
b)实施方案1-13中任一项所述的药物组合，其被制备为适合在第二治疗阶段施用。
实施方案43.根据实施方案42所述的联用药物组合，其中，所述第一治疗阶段包括1-14个治疗周期、2-12个治疗周期或2-10个治疗周期，优选2-8个治疗周期，更优选4-6个治疗周期。
实施方案44.根据实施方案43所述的联用药物组合，其中，每1周、每2周、每3周、或每4周为一个治疗周期，优选地，每3周为一个治疗周期。
实施方案45.实施方案42-44中任一项所述的联用药物组合在制备用于治疗受试者中肿瘤的药物中的用途。
实施方案46.根据实施方案45所述的用途，其中，所述肿瘤为头颈癌；优选地，所述肿瘤为头颈鳞状细胞癌；优选地，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞状细胞癌。
实施方案47.根据实施方案46所述的用途，其中，所述头颈鳞状细胞癌的主体既往未接受过系统治疗以治疗头颈鳞状细胞癌。
实施方案48.根据实施方案45所述的用途，其中，所述肿瘤为食管癌；优选地，所述肿瘤为食管鳞状细胞癌；优选地，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌。
实施方案49.根据实施方案48所述的用途，其中，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
实施方案50.抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中，所述抗TIM-3抗体或其抗原结合片段包含：
SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或
SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3。
实施方案51.抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物在制备用于治疗受试者中肿瘤的药物中的用途，其中，所述抗TIM-3抗体或其抗原结合片段包含：
SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或
SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3；
可选地，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物；
可选地，所述铂类抗肿瘤药物选自顺铂、卡铂、奈达铂、双环铂、吡铂、奥沙利铂、米铂、洛铂、乐铂、四硝酸三铂、菲铂和沙铂中的一种或多种；
可选地，所述紫杉烷类抗肿瘤药物选自紫杉醇、卡巴他赛和多西他赛中的一种或多种；
可选地，所述化疗药物为顺铂和紫杉醇，或者，所述化疗药物为卡铂和紫杉醇。
实施方案52.根据实施方案50或51所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段包含：
氨基酸序列与SEQ ID NO:7所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:8所示氨基酸序列具有至少95％同一性的轻链可变区；或
氨基酸序列与SEQ ID NO:27所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:28所示氨基酸序列具有至少95％同一性的轻链可变区。
实施方案53.根据实施方案50-52中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段包含：
氨基酸序列与SEQ ID NO:9所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:10所示氨基酸序列具有至少95％同一性的轻链；或
氨基酸序列与SEQ ID NO:29所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:30所示氨基酸序列具有至少95％同一性的轻链。
实施方案54.根据实施方案50-53中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3。
实施方案55.根据实施方案50-54中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:17所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:18所示氨基酸序列具有至少95％同一性的轻链可变区。
实施方案56.根据实施方案50-55中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段 包含：氨基酸序列与SEQ ID NO:19所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:20所示氨基酸序列具有至少95％同一性的轻链。
实施方案57.根据实施方案50-56中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于胃肠外施用的制剂，优选地，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于静脉内、肌肉内或皮下施用的制剂。
实施方案58.根据实施方案50-57中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中。
实施方案59.根据实施方案50-58中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段分开配制。
实施方案60.根据实施方案50-59中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段的单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg；优选地，所述抗TIM-3抗体或其抗原结合片段的单位剂量为240mg、300mg、360mg和/或600mg。
实施方案61.根据实施方案50-60中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段的单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg；优选地，所述抗PD-1抗体或其抗原结合片段的单位剂量为100mg和/或200mg。
实施方案62.根据实施方案50-61中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的质量比为(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1。
实施方案63.根据实施方案50-62中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，可同时、先后和/或交替给药。
实施方案64.根据实施方案50-62中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇，可同时、先后和/或交替给药；或者所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇，可同时、先后和/或交替给药。
实施方案65.根据实施方案50-64中任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗TIM-3抗体或其抗原结合片段每3周施用一次；可选地，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用，优选地，所述抗TIM-3抗体或其抗原结合片段每次以1200mg的剂量施用。
实施方案66.根据实施方案50-65中任一项所述的用途，其中，所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗PD-1抗体或其抗原结合片段每3周施用一次；可选地，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用，优选地，所述抗PD-1抗体或其抗原结合片段每次以200mg的剂量施用。
实施方案67.根据实施方案50-66中任一项所述的用途，其中，所述顺铂每1周、每2周、每3周、或每4周施用一次，优选地，所述顺铂每3周施用一次；可选地，所述顺铂每次以30-100mg/m2、30-75mg/m2、48-75mg/m2或60-75mg/m2的剂量施用，优选地，所述顺铂每次以60-75mg/m2的剂量施用；或者所述卡铂每1周、每2周、每3周、或每4周施用一次，优选地，所述卡铂每3周施用一次；可选地，所述卡铂每次以2.5-5mg/(mL/min)AUC或3.2-5mg/(mL/min)AUC的剂量施用，优选地，所述卡铂每次以3.2-5mg/(mL/min)AUC的剂量施用。
实施方案68.根据实施方案50-67中任一项所述的用途，其中，所述紫杉醇每1周、每2周、每3周、或每4周施用一次，优选地，所述紫杉醇每3周施用一次；可选地，所述紫杉醇每次以75-175mg/m2、100-175mg/m2、112-175mg/m2或135-175mg/m2的剂量施用，优选地，所述紫杉醇每次以135-175mg/m2的剂量施用。
实施方案69.根据实施方案50-68中任一项所述的用途，其中，所述肿瘤为头颈癌；优选地，所述肿瘤为头颈鳞状细胞癌；优选地，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞状细胞癌。
实施方案70.根据实施方案69所述的用途，其中，所述头颈鳞状细胞癌的主体既往未接受过系统治疗以治疗头颈鳞状细胞癌。
实施方案71.根据实施方案50-68中任一项所述的用途，其中，所述肿瘤为食管癌；优选地，所述肿瘤为食管鳞状细胞癌；优选地，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌。
实施方案72.根据实施方案71所述的用途，其中，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
技术效果
通常，使用上述的本公开的药物组合将有助于：
(1)与单独给予该组合中的任一药物相比，在减少肿瘤的生长或甚至消除肿瘤方面产生更好的疗效；
(2)与该组合中的任一药物单独给药相比，提供更少量的给药；
(3)提供在患者中具有良好耐受的治疗，与单一给予的任一药物相比，其不良反应和/或并发症更少；
(4)提供在所治疗患者之中的更好的疾病控制率；
(5)提供在所治疗的患者具有更长的生存期(例如中位生存期、无进展生存期或总生存期)；
(6)提供相比于标准的化疗而言，所治疗患者具有更长的生存期(例如中位生存期、无进展生存期或总生存期)；
(7)提供更长时间的疾病缓解持续时间(DOR)；和/或
(8)与单独给予该组合中的任一药物相比，具有良好的抗肿瘤的活性，表现出更优异的抗肿瘤协同效果。
本公开的药物组合及治疗方案，在治疗头颈癌尤其是复发性或转移性头颈部鳞状细胞中具有较好的疗效。其中至少在ORR、DCR、DOR、PFS、9个月PFS率、6个月PFS率、OS、耐受性和副作用中的至少一方面具有有益的效果，例如，提高患者9个月PFS率和/或6个月PFS率。
本公开的药物组合及治疗方案，在治疗食管癌尤其是不可切除的局部晚期、复发性或转移性食管鳞癌中具有较好的疗效。其中至少在ORR、DCR、DOR、PFS、9个月PFS率、6个月PFS率、OS、耐受性和副作用中的至少一方面具有有益的效果，例如，提高患者ORR、PFS、9个月PFS率和/或6个月PFS率。
定义和说明
除非另有说明，本公开中所用的下列术语具有下列含义。一个特定的术语在没有特别定义的情况下不应该被认为是不确定的或不清楚的，而应该按照本领域普通的含义去理解。当本公开中出现商品名时，意在指代其对应的商品或其活性成分。
如文本所用，术语“药物组合”是指同时或先后施用的两种或两种以上的活性成分(包括以各自的活性成分本身的形式施用，或者以其各自的药学上可接受的盐或酯等衍生物、前药或组合物的形式施用)的组合。所述活性成分可以各自作为单一制剂同时地、或各自作为单一制剂以任何顺序依次地施用于受试者。或者，所述活性成分的全部配制在单一制剂中，同时施用于受试者。或者，所述活性成分的部分配制在单一制剂中、且所述活性成分中的其他部分各自作为单一制剂，同时地、或以任何顺序依次地施用于受试者。
术语“固定组合”指活性组分以固定总剂量或剂量比例，或以单一实体、药物组合物或制剂的形式同时给予受试者。
术语“非固定组合”指两种以上活性组分作为独立的实体(例如药物组合物、制剂)同时、并行或依序地给予受试者，其中所述给予受试者的活性成份达到治疗有效量水平。非固定组合可列举的例子是鸡尾酒疗法，例如给予3种或以上之活性组分。在非固定组合中，所述各个活性组分可以作为完全独立的药物组合物进行包装、销售或给药。所述“非固定组合”也包括“固定组合”之间、或“固定组合”与任一或多种活性组分的独立实体的联合使用。
如本文所用，术语“抗体”是指具有至少一个抗原结合结构域的抗原结合蛋白。本公开的抗体和其片段可以是整个抗体或其任何片段。因此，本公开的抗体和其片段包括单克隆抗体或其片段和抗体变体或其片段。抗体和其抗原结合片段片段的实例包括单特异性抗体、双特异性抗体、多特异性抗体、Fab片段、Fab'片段、F(ab)'2片段、Fv片段、分离的CDR区、单链Fv分子(scFv)和本领域已知的其它抗体片段。本文公开的抗TIM-3抗体和抗PD-1抗体和其抗原结合片段可以是IgG1、IgG2、IgG3或IgG4同种型。术语“同种型”是指由重链恒定区基因编码的抗体种类。本公开的抗TIM-3抗体和其抗原结合片段以及抗PD-1抗体和其抗原结合片段可以衍生自任何物种，包括但不限于小鼠、大鼠、兔、灵长类动物、美洲驼和人。本公开的抗TIM-3抗体和其抗原结合片段以及抗PD-1抗体和其抗原结合片段可以是鼠类抗体、嵌合抗体、人源化抗体或全人源抗体。除非另有说明，否则本公开的“抗体”包括整个抗体及其任何抗原结合片段(或“抗 原结合部分”)或单链。常规的“整个抗体”是包含两条重(H)链和两条轻(L)链的糖蛋白，重链和轻链通过二硫键连接。每条重链由重链可变区(VH)和重链恒定区(CH)组成。重链恒定区由三个结构域组成，即CH1，CH2和CH3。每条轻链由轻链可变区(VL)和轻链恒定区(CL)组成。轻链恒定区由一个结构域CL组成。VH和VL区还可以划分为高变区，即互补决定区(CDR)，和序列较为保守的框架区(FR)。每个VH和VL分别由三个CDR和四个FR组成，从氨基端到羧基端分别为：FR1，CDR1，FR2，CDR2，FR3，CDR3，FR4。重链和轻链的可变区包含与抗原相互作用的结合域。抗体的恒定区可以介导免疫球蛋白与宿主组织或因子的结合，所述宿主组织或因子包括免疫系统的多种细胞(例如，效应细胞)和经典补体系统的第一成分(C1q)。与此同时，如本领域技术人员所了解的，特殊的“整个抗体”，例如纳米抗体，其仅只有重(H)链而没有轻(L)链。
抗体的“抗原结合片段”或“抗体结合部分”是指抗体的一个或多个片段，其保留特异性结合抗原(例如，TIM-3或PD-1)的功能。已证实，抗体的抗原结合功能可以通过整个抗体的片段来实施。涵盖在术语抗体的“抗原结合部分/片段”中的实例包括：(i)Fab片段：由VL、VH、CL和CH1结构域组成的单价片段；(ii)F(ab')2片段，包含在铰链区二硫桥连接的两个Fab片段的二价片段；(iii)由VH和CH1结构域组成的Fd片段；(iv)由抗体单臂的VL和VH结构域组成的Fv片段；(v)由VH结构域组成的dAb片段(参见Ward et al.,Nature.341:544-546(1989))；(vi)分离的互补决定区(CDR)；以及(vii)纳米抗体，一种包含单可变结构域和两个恒定结构域的重链可变区。此外，尽管Fv片段的两个结构域VL和VH由不同基因编码，但可以采用重组的方法通过合成接头将VH和VL连接成单蛋白链，其中VL和VH配对形成单价分子(称单链Fv(scFv)；参见例如Bird et al.,Science.242:423-426(1988)；Huston et al.,Proc.Natl.Acad.Sci.85:5879-5883(1988))。这些单链抗体也涵盖在术语抗原结合部分/片段中。此外，包含该抗原结合部分/片段的重组多肽、融合蛋白和免疫缀合物也涵盖在术语抗原结合部分/片段中。
“嵌合抗体”是下述抗体：所述抗体具有衍生自一种物种的重链可变区的至少一部分和轻链可变区的至少一部分；以及衍生自另一物种的恒定区的至少一部分。例如，在一个实施方案中，嵌合抗体可以包含鼠类可变区和人恒定区。
“人源化抗体”是下述抗体：所述抗体含有衍生自非人抗体的互补决定区(CDR)，以及衍生自人抗体的框架区和恒定区。例如，抗TIM-3抗体以及抗PD-1抗体可以包含衍生自一种或多种鼠类抗体的CDR以及人框架区和人恒定区。本文提供了示例性人源化抗体。包含本文提供的HCDR和LCDR的另外的抗TIM-3抗体或其变体可以使用任何人框架序列产生，并且也包括在本公开中。包含本文提供的HCDR和LCDR的另外的抗PD-1抗体或其变体可以使用任何人框架序列产生，并且也包括在本公开中。在一个实施方案中，适用于在本公开中使用的框架序列包括在结构上与本文提供的框架序列类似的那些框架序列。可以在框架区中进行另外修饰以改进本文提供的抗体的特性。此类另外的框架修饰可以包括化学修饰；点突变以降低免疫原性或去除T细胞表位；或使突变回复为原始种系序列中的残基。在一些实施方案中，此类修饰包括对应于本文示例的突变的那些修饰，包括对种系序列的回复突变。例如，在一个实施方案中，本文提供的人源化抗体的VH和/或VL的人框架区中的一个或多个氨基酸被回复突变为亲本鼠类抗体中对应的氨基酸。
术语“同一性”，也称一致性。氨基酸序列的“同一性百分数(％)”是指将待比对序列与本文中所示的具体氨基酸序列进行比对并且如有必要的话为达到最大序列同一性百分数而引入空位后，并且不考虑任何保守置换作为序列同一性的一部分时，待比对序列中与本文中所示的具体氨基酸序列的氨基酸残基相同的氨基酸残基百分数。同一性的氨基酸序列比对可以采用本领域范围内的多种方式进行，例如BLAST、BLAST-2、ALIGN或Megalign(DNASTAR)软件。本领域技术人员可决定用于比对序列的适宜参数，包括在比较序列的全长里获得最大比对需要的任何算法。
术语“治疗”一般是指获得需要的药理和/或生理效应的操作。该效应根据完全或部分地预防疾病或其症状，可以是预防性的；和/或根据部分或完全地稳定或治愈疾病和/或由疾病产生的副作用，可以是治疗性的。本文使用的“治疗”涵盖了对患者疾病的任何治疗，包括但不限于预防疾病的发生或复发，缓解疾病的症状，降低疾病的任何直接或间接病理学后果，预防疾病的转移，减缓疾病的进展，改善或减轻疾病的状态，延长无症状期频率和持续时间，及消退或改善疾病的预后。
“治疗有效量”或“治疗上有效的剂量”是当单独使用或与另一种或多种治疗剂联合使用时保护主体免于 疾病发作或促进疾病消退的药物的任何量，所述疾病消退通过疾病症状的严重程度的降低、无疾病症状期的频率和持续时间的增加、或由疾病折磨引起的损伤或失能的预防来证明。使用熟练的从业人员已知的多种方法可以评价治疗剂的促进疾病消退的能力，诸如在临床试验期间在人主体中，在预测对于人类的效力的动物模型系统中，或通过在体外测定法中测定所述药剂的活性。
如本文所用，“治疗阶段”是指向受试者施用药物组合(例如，包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的药物组合，或者包括抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物(例如，顺铂和紫杉醇，或者卡铂和紫杉醇)的药物组合)的一段时期。“第一治疗阶段”即初始治疗阶段，可以是诱导治疗阶段，“第二治疗阶段”即第一治疗阶段结束之后的治疗阶段，可以是维持治疗阶段。
术语“施用”、“给药”或“给予”表示，使用本领域技术人员已知的多种方法和递送系统中的任一种，向主体物理引入治疗剂。
抗体或其抗原结合片段(例如，抗TIM-3抗体或其抗原结合片段或抗PD-1抗体或其抗原结合片段)的施用途径包括静脉内、肌肉内、皮下、腹膜内、脊柱或其它胃肠外施用途径，例如通过注射或输注。本文中使用的短语“胃肠外施用”是指，通常通过注射进行的除了胃肠内施用以外的施用模式，且包括但不限于，静脉内、肌肉内、动脉内、鞘内、淋巴管内、病灶内、囊内、眶内、心内、真皮内、腹膜内、经气管、皮下、表皮下、关节内、囊下、蛛网膜下、脊柱内、硬膜外和胸骨内注射和输注、以及体内电穿孔。还可以执行施用，例如，一次、多次，和/或在一个或多个延长的时间段中。
术语“统一剂量(flat dose)”的应用是指，不考虑患者的重量或体表面积(BSA)施用给患者的剂量。因此将统一剂量规定为药剂(例如，抗TIM-3抗体或其抗原结合片段)的绝对量，而不是规定为mg/kg剂量。例如，60kg人和100kg人将接受相同剂量的抗体(例如，1200mg抗TIM-3抗体或其抗原结合片段)。
术语“药学上可接受的”，是针对那些化合物、材料、组合物和/或剂型而言，它们在可靠的医学判断的范围之内，适用于与人类和动物的组织接触使用，而没有过多的毒性、刺激性、过敏性反应或其它问题或并发症，与合理的利益/风险比相称。
术语“药物组合物”是指一种或多种本公开的活性成分或其药物组合与药学上可接受的载体组成的混合物。药物组合物的目的是有利于对受试者给予本公开的化合物或其药物组合。在本文中，术语“药物组合物”和“制剂”具有相同的含义，并可互换使用。
在本文中，术语“受试者”、“患者”或“主体”可互换使用。“受试者”、“患者”或“主体”包括任何人或非人动物。术语“非人动物”包括但不限于脊椎动物诸如非人灵长类动物、绵羊、狗，和啮齿类动物诸如小鼠、大鼠和豚鼠。在一些实施方案中，术语“受试者”、“患者”或“主体”是哺乳动物。在部分实施方案中，所述受试者、患者或主体是小鼠。在部分实施方案中，所述受试者、患者或主体是人。
如本文所用，“联用”或“联合使用”意指两种或更多种活性物质可以各自作为单一制剂同时地、或各自作为单一制剂以任何顺序依次地施用于受试者。或者，所述活性成分的全部配制在单一制剂中，同时施用于受试者。或者，所述活性成分的部分配制在单一制剂中、且所述活性成分中的其他部分各自作为单一制剂，同时地、或以任何顺序依次地施用于受试者。
术语“单剂量”是指含有一定量药品的最小包装单元，例如一盒药有七粒药片，则一粒药片为单剂量；或者一瓶注射液为单剂量。术语“多剂量”由多个单剂量组成。“单位剂量”是指含有一定量药品的最小包装单元中所含的活性成分的剂量，例如，一瓶抗体注射液中所含的抗体的剂量为单位剂量。
术语“复发性”癌症是在对初始治疗(例如手术)产生应答后，在初始部位或远处部位再生的癌症。“局部复发性的”癌症是在治疗后，在与先前治疗的癌症相同的位置出现的癌症。
术语“转移性”癌症是指从身体的一部分(例如口腔)扩散到身体的另一部分的癌症。
术语“难治性”是指受试者或哺乳动物即使在强烈治疗后在其体内也具有残留癌细胞的情况。
如本文所用，“治疗失败”的定义为在治疗过程中或末次治疗后出现疾病进展或复发、或治疗过程中因为毒副作用不可耐受。
术语“一线治疗”是指是指根据患者病情可以首先选择或者标准选择的药物进行治疗。
词语“包括(comprise)”、“含有(comprise)”或“包含(comprise)”及其英文变体例如comprises或comprising应理解为开放的、非排他性的意义，即“包括但不限于”。
在本文中，除非上下文另有明确规定，否则单数术语涵盖复数指代物，反之亦然。
如本文所用，“约”表示在本领域普通技术人员判定的对特定值可以接受的误差范围内，其部分取决于如何测量或测定该值，即测量系统的限制。例如，“约”按照本领域实践可表示1倍或超过1倍标准偏差以内。或者，“约”可以表示多至±5％的范围，例如在所给定的具体数值范围±2％范围内、±1％范围内或±0.5％范围内波动。当本公开或权利要求中给出特定值时，除非另有说明，“约”的含义应认为是在该特定值的可接受的误差范围内。在本文中，除非另有说明，所有药物的剂量、时间、步骤参数或条件的值默认均由“约”修饰。
为了描述和公开的目的，以引用的方式将所有的专利、专利申请和其它已确定的出版物在此明确地并入本文。这些出版物仅因为它们的公开早于本公开的申请日而提供。所有关于这些文件的日期的声明或这些文件的内容的表述是基于申请者可得的信息，并且不构成任何关于这些文件的日期或这些文件的内容的正确性的承认。而且，在任何国家，在本中对这些出版物的任何引用并不构成关于该出版物成为本领域的公知常识的一部分的认可。
实施例
为清楚起见，进一步用实施例来阐述本公开，但是实施例并非限制本公开的范围。本公开所使用的所有试剂是市售的，无需进一步纯化即可使用。
WO2020041520或CN112566936专利申请文件的全部内容均引入本公开。下述实施例中抗TIM-3抗体的重链氨基酸序列如本公开的SEQ ID NO:9所示，和轻链氨基酸序列如本公开的SEQ ID NO:10所示。
CN106977602A专利申请文件的全部内容均引入本公开。下述实施例中抗PD-1抗体的重链氨基酸序列如本公开的SEQ ID NO:19所示，和轻链氨基酸序列如本公开的SEQ ID NO:20所示。
实施例1：头颈鳞癌的临床试验
1.入选标准
满足以下所有入选标准者才能入组本试验：
(1)受试者自愿加入本研究，签署知情同意书(ICF)，依从性好；
(2)年龄：18-75周岁(签署ICF时)；ECOG PS评分：0-1分；预计生存期超过3个月；
(3)无局部根治性治疗指征的，经组织学或细胞学确诊的复发性或转移性头颈部鳞状细胞(R/M HNSCC)受试者，原发部位为口腔、口咽部、下咽、喉部或鼻腔/鼻窦；
(4)未接受过针对复发性或转移性灶的系统治疗，但不包括作为多模式治疗的一个环节针对局部晚期疾病进行的系统治疗(包括诱导治疗、放疗同期的系统治疗及辅助治疗)且治疗完成时间距入组(以知情同意日期计)超过6个月；
(5)根据RECIST 1.1标准证实具有至少一个可测量病灶；
(6)主要器官功能正常，即符合下列标准：
1)血常规检查标准(筛选前7天内未输血、未使用造血刺激因子类药物纠正)：
a.血红蛋白(HGB)≥90g/L；
b.中性粒细胞绝对值(NEUT)≥1.5×109/L；
c.血小板计数(PLT)≥90×109/L；
2)生化检查需符合以下标准：
a.血清总胆红素(TBIL)≤1.5倍正常值上限(ULN)；
b.丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)≤2.5×ULN(如有肝脏转移者：ALT、AST≤5×ULN)；
c.血清肌酐(CR)≤1.5×ULN或肌酐清除率(CCR)≥60mL/min(Cockcroft Gault公式)；
3)凝血功能或甲状腺功能检查需符合以下标准：
a)国际标准化比值(INR)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)≤1.5倍ULN(未接受过抗凝治疗)；
b)促甲状腺激素(TSH)≤ULN；如果异常应考察三碘甲腺原氨酸(T3)和四碘甲腺原氨酸(T4)水平，T3和T4水平正常则可以入选。
4)心脏彩超评估：左室射血分数(LVEF)≥50％。
(7)育龄女性受试者应同意在研究期间和研究结束后6个月内必须采用避孕措施(如宫内节育器、避孕药或避孕套)；在研究入组前的7天内血清妊娠试验阴性，且必须为非哺乳期受试者；男性受试者应同意在研究期间和研究期结束后6个月内必须采用避孕措施。
2.试验药物
2.1抗PD-1抗体注射液(规格：100mg/10mL/瓶，由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期(给药时间窗：±3天)，通过静脉输注，每个治疗周期的第1天以200mg抗PD-1抗体的剂量给药一次。
2.2抗TIM-3抗体注射液(规格：240mg/4mL/瓶、或600mg/10mL/瓶，由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期(给药时间窗：±3天)，通过静脉输注，每个治疗周期的第1天以1200mg抗TIM-3抗体的剂量给药一次。
2.3紫杉醇(由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期，通过静脉输注，每个治疗周期的第1天以175mg/m2紫杉醇的剂量施用一次。
2.4顺铂(由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期，通过静脉输注，每个治疗周期的第1天以75mg/m2顺铂的剂量施用一次。
2.5卡铂(由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期，通过静脉输注，每个治疗周期的第1天以5mg/(mL/min)AUC的剂量施用一次。
卡铂的给药剂量需要按血药浓度-时间曲线下面积(AUC)和内生肌酐清除率来计算。AUC(mg/(mL/min))取值为5。
卡铂给药剂量(mg)＝所设定的AUC(mg/(mL/min))×[肌酐清除率(mL/min)+25]
肌酐清除率采用Cockcroft-Gault公式计算：

3.治疗方案
第一治疗阶段(初始治疗阶段)：抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂，或者抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+卡铂；治疗4-6个治疗周期。给药顺序：抗PD-1抗体注射液→抗TIM-3抗体注射液→紫杉醇→顺铂或卡铂。
第二治疗阶段(维持治疗阶段)：抗TIM-3抗体注射液+抗PD-1抗体注射液，治疗直至疾病进展或毒性不能耐受。给药顺序：抗PD-1抗体注射液→抗TIM-3抗体注射液。
第二治疗阶段在第一治疗阶段之后。
4.给药方案调整
PD-1抗体注射液：允许延迟用药，但延迟用药时间最长不能超过12周。
抗TIM-3抗体注射液：允许延迟用药，但延迟用药时间最长不能超过12周。
5.评价标准
疗效评估标准依据RECIST 1.1，同时使用iRECIST标准对疗效进行确认。采用NCI-CTC AE 5.0标准判断不良事件严重程度。
6.终点指标
客观缓解率(ORR)、无进展生存期(PFS)、9个月PFS率、6个月PFS率、总生存期(OS)、疾病控制率(DCR＝＝CR+PR+SD)、临床获益率(CBR)、缓解持续时间(DOR)等；
不良事件发生率：所有不良事件(AE)和严重不良事件(SAE)的发生率和严重程度，以及异常实验室检查指标。
7.结果
初步研究显示，抗TIM-3抗体、抗PD-1抗体、紫杉醇联合顺铂或卡铂可以安全有效地治疗复发性或转移性头颈部鳞状细胞，提升患者的临床疗效和生存获益，延长患者的无进展生存期，提高9个月和6个 月PFS率。截至数据统计日，有13例可评估患者，其中，6例患者观察到部分反应(PR)，6例患者表现出疾病稳定(SD)，ORR达到46.2％，DCR为92.3％。示例性患者的具体情况如下所示。
(1)患者1
被诊断为：口腔癌。
既往治疗史：经手术治疗。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗6个治疗周期后，抗TIM-3抗体注射液+抗PD-1抗体注射液维持治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：54.91mm；
治疗2个治疗周期，靶病灶：43.01mm；
治疗4个治疗周期，靶病灶：13.47mm；
治疗6个治疗周期，靶病灶：5mm；
治疗8个治疗周期，靶病灶：5mm；
根据疗效评估标准，患者的最佳疗效为PR。
(2)患者2
被诊断为：喉癌。
既往治疗史：经手术治疗、放射疗法。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：34.25mm；
治疗2个治疗周期，靶病灶：26.33mm；
治疗4个治疗周期，靶病灶：20.36mm；
根据疗效评估标准，患者的最佳疗效为PR。
(3)患者3
被诊断为：舌癌。
既往治疗史：无。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：30.06mm；
治疗2个治疗周期，靶病灶：17.4mm；
治疗4个治疗周期，靶病灶：10.94mm；
治疗6个治疗周期，靶病灶：10.3mm；
根据疗效评估标准，患者的最佳疗效为PR。
(4)患者4
被诊断为：左颌鳞状细胞癌。
既往治疗史：无。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：38.52mm；
治疗2个治疗周期，靶病灶：25.07mm；
治疗4个治疗周期，靶病灶：15.9mm；
治疗6个治疗周期，靶病灶：9.4mm；
根据疗效评估标准，患者的最佳疗效为PR。
(5)患者5
被诊断为：喉癌。
既往治疗史：经手术治疗、放射治疗。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+卡铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：37.4mm；
治疗2个治疗周期，靶病灶：20mm；
治疗4个治疗周期，靶病灶：16.8mm；
治疗6个治疗周期，靶病灶：16.6mm；
根据疗效评估标准，患者的最佳疗效为PR。
(6)患者6
被诊断为：口腔癌。
既往治疗史：经帕博利珠单抗+紫杉醇+卡铂治疗治疗2个周期后行手术治疗、放射疗法。
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：22.4mm；
治疗2个治疗周期，靶病灶：18.8mm；
治疗4个治疗周期，靶病灶：12.7mm；
根据疗效评估标准，患者的最佳疗效为PR。
实施例2：食管鳞癌的临床试验
1.入选标准
满足以下所有入选标准者才能入组本试验：
(1)受试者自愿加入本研究，签署知情同意书(ICF)，依从性好；
(2)年龄：18-75周岁(签署ICF时)；ECOG PS评分：0-1分；预计生存期超过3个月；
(3)经组织病理学或细胞学确诊的不可切除的局部晚期、复发性或转移性食管鳞癌(不包括腺鳞癌混合型)；(4)既往未接受过系统治疗，或(新)辅助治疗/根治性放化疗结束6个月以上复发者；
(5)根据RECIST 1.1标准证实具有至少一个可测量病灶；
(6)主要器官功能正常，即符合下列标准：
1)血常规检查标准(检查前14天内未输血、未使用造血刺激因子类药物纠正)：
d.血红蛋白(HGB)≥90g/L；
e.中性粒细胞计数(ANC)≥1.5×109/L；
f.血小板计数(PLT)≥100×109/L；
2)生化检查需符合以下标准：
d.血清总胆红素(TBIL)≤1.5倍正常值上限(ULN)；
e.丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)≤2.5×ULN(如有肝脏转移者：ALT、AST≤5×ULN)；
f.血清肌酐(CR)≤1.5×ULN或肌酐清除率(CCR)≥60mL/min(Cockcroft Gault公式)；
3)凝血功能或甲状腺功能检查需符合以下标准：
a)国际标准化比值(INR)、凝血酶原时间(PT)≤1.5倍ULN；
b)促甲状腺激素(TSH)≤ULN；如果异常应考察T3和T4水平，T3和T4水平正常则可以入选。
4)心脏彩超评估：左室射血分数(LVEF)≥50％。
(7)育龄女性受试者应同意在研究期间和研究结束后6个月内必须采用避孕措施(如宫内节育器、避孕药或避孕套)；在研究入组前的7天内血清妊娠试验阴性，且必须为非哺乳期受试者；男性受试者应同意在研究期间和研究期结束后6个月内必须采用避孕措施。
2.试验药物
2.1抗PD-1抗体注射液(规格：100mg/10mL/瓶，由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期(给药时间窗：±3天)，通过静脉输注，每个治疗周期的第1天以200mg抗PD-1抗体的剂量给药一次。
2.2抗TIM-3抗体注射液(规格：240mg/4mL/瓶、或600mg/10mL/瓶，由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期(给药时间窗：±3天)，通过静脉输注，每个治疗周期的第1天以1200mg抗TIM-3抗体的剂量给药一次。
2.3紫杉醇(由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期，通过静脉输注，每个治疗周期的第1天以135-150mg/m2紫杉醇的剂量施用一次。
2.4顺铂(由正大天晴药业集团股份有限公司提供)：3周为1个治疗周期，通过静脉输注，每个治疗周期的第1天以60-75mg/m2顺铂的剂量施用一次。
3.治疗方案
第一治疗阶段(初始治疗阶段)：抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂；治疗4-6个治疗周期。给药顺序：先施用PD-1抗体注射液，再施用抗TIM-3抗体注射液，顺铂在紫杉醇之后施用。
第二治疗阶段(维持治疗阶段)：抗TIM-3抗体注射液+抗PD-1抗体注射液，治疗直至疾病进展或毒性不能耐受。给药顺序：抗PD-1抗体注射液→抗TIM-3抗体注射液。
第二治疗阶段在第一治疗阶段之后。
4.给药方案调整
PD-1抗体注射液：允许延迟用药，但延迟用药时间最长不能超过12周。
抗TIM-3抗体注射液：允许延迟用药，但延迟用药时间最长不能超过12周。
5.评价标准
疗效评估标准依据RECIST 1.1，同时使用iRECIST标准对疗效进行确认。采用NCI-CTC AE 5.0标准判断不良事件严重程度。
8.终点指标
客观缓解率(ORR)、无进展生存期(PFS)、9个月PFS率、6个月PFS率、总生存期(OS)、疾病控制率(DCR＝CR+PR+SD)、缓解持续时间(DOR)等；
不良事件发生率：所有不良事件(AE)和严重不良事件(SAE)的发生率和严重程度，以及异常实验室检查指标。
6.结果
初步研究显示，抗TIM-3抗体、抗PD-1抗体、紫杉醇联合顺铂可以安全有效地治疗不可切除的局部晚期、复发性或转移性食管鳞癌，提升患者的临床疗效和生存获益，延长患者的无进展生存期，提高9个月和6个月PFS率。截至数据统计日，有19例患者完成至少2个治疗周期，患者的最佳疗效见表3。
表3.完成至少2个治疗周期后的最佳疗效汇总(N＝19)
示例性患者的具体情况如下所示。
(1)患者1
被诊断为：食管鳞癌
既往治疗史：食管癌根治术
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂初始治疗，抗PD-1抗体注射液+抗TIM-3抗体注射液维持治疗。靶病灶大小和评估结果如下所示：
筛选期，淋巴结靶病灶：15.2mm；
治疗2个治疗周期，淋巴结靶病灶：8mm；
治疗4个治疗周期，淋巴结靶病灶：8mm；
治疗6个治疗周期，淋巴结靶病灶：8.8mm；
治疗8个治疗周期，淋巴结靶病灶：8.5mm；
根据疗效评估标准，患者的最佳疗效为CR。
(2)患者2
被诊断为：食管鳞癌
既往治疗史：无
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂初始治疗，抗PD-1抗体注射液+抗TIM-3抗体注射液维持治疗。靶病灶大小和评估结果如下所示：
筛选期，淋巴结靶病灶：30mm；
治疗2个治疗周期，淋巴结靶病灶：17mm；
治疗4个治疗周期，淋巴结靶病灶：16mm；
治疗6个治疗周期，淋巴结靶病灶：16mm；
治疗8个治疗周期，淋巴结靶病灶：16mm；
根据疗效评估标准，患者的最佳疗效为PR。
(3)患者3
被诊断为：食管鳞癌
既往治疗史：无
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，靶病灶：76.71mm；
治疗2个治疗周期，淋巴结靶病灶：41.16mm；
治疗4个治疗周期，淋巴结靶病灶：29.08mm；
根据疗效评估标准，患者的最佳疗效为PR。
(4)患者4
被诊断为：食管鳞癌
既往治疗史：无
经抗TIM-3抗体注射液+抗PD-1抗体注射液+紫杉醇+顺铂治疗。靶病灶大小和评估结果如下所示：
筛选期，淋巴结靶病灶：137.3mm；
治疗2个治疗周期，淋巴结靶病灶：79.7mm；
治疗4个治疗周期，淋巴结靶病灶：62.3mm；
根据疗效评估标准，患者的最佳疗效为PR。

Claims (15)

  1. 一种药物组合，其包括抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，其中，
    所述抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3；
    所述抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3。
  2. 根据权利要求1所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于胃肠外施用的制剂，优选地，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制为用于静脉内、肌肉内或皮下施用的制剂。
  3. 根据权利要求1或2所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段配制在单一制剂中或分开配制。
  4. 根据权利要求1-3任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段的单位剂量为60-1800mg、100-1600mg、120-1600mg、180-1200mg、或240-600mg；优选地，所述抗TIM-3抗体或其抗原结合片段的单位剂量为240mg、300mg、360mg和/或600mg；和/或
    所述抗PD-1抗体或其抗原结合片段的单位剂量为10-500mg、50-500mg、50-200mg、或100-200mg；
    优选地，所述抗PD-1抗体或其抗原结合片段的单位剂量为100mg和/或200mg。
  5. 根据权利要求1-4任一项所述的药物组合，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段的质量比为(0.1-180):1、(0.2-50):1、(0.5-9):1、(3-7.5):1、(4-7.5):1或(6-7.5):1。
  6. 根据权利要求1-5任一项所述的药物组合，其中，所述药物组合还包括化疗药物；优选地，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物；
    可选地，所述铂类抗肿瘤药物选自顺铂、卡铂、奈达铂、双环铂、吡铂、奥沙利铂、米铂、洛铂、乐铂、四硝酸三铂、菲铂和沙铂中的一种或多种；
    可选地，所述紫杉烷类抗肿瘤药物选自紫杉醇、卡巴他赛和多西他赛中的一种或多种；
    可选地，所述化疗药物为顺铂和紫杉醇，或者，所述化疗药物为卡铂和紫杉醇。
  7. 根据权利要求1-6任一项所述的药物组合，其中，所述药物组合适用于在单个治疗周期内施用，其包括100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的抗TIM-3抗体或其抗原结合片段；和/或10-800mg、50-500mg、或100-200mg的抗PD-1抗体或其抗原结合片段。
  8. 根据权利要求1-7任一项所述的药物组合在制备用于治疗受试者中肿瘤的药物中的用途。
  9. 抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段在制备用于治疗受试者中肿瘤的药物中的用途，其中，
    所述抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3；
    所述抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3。
  10. 抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段和化疗药物在制备用于治疗受试者 中肿瘤的药物中的用途，其中，
    所述抗TIM-3抗体或其抗原结合片段包含：SEQ ID NO:1所示氨基酸序列的HCDR1，SEQ ID NO:2所示氨基酸序列的HCDR2，SEQ ID NO:3所示氨基酸序列的HCDR3，SEQ ID NO:4所示氨基酸序列的LCDR1，SEQ ID NO:5所示氨基酸序列的LCDR2，和SEQ ID NO:6所示氨基酸序列的LCDR3；或SEQ ID NO:21所示氨基酸序列的HCDR1，SEQ ID NO:22所示氨基酸序列的HCDR2，SEQ ID NO:23所示氨基酸序列的HCDR3，SEQ ID NO:24所示氨基酸序列的LCDR1，SEQ ID NO:25所示氨基酸序列的LCDR2，和SEQ ID NO:26所示氨基酸序列的LCDR3；
    所述抗PD-1抗体或其抗原结合片段包含：SEQ ID NO:11所示氨基酸序列的HCDR1，SEQ ID NO:12所示氨基酸序列的HCDR2，SEQ ID NO:13所示氨基酸序列的HCDR3，SEQ ID NO:14所示氨基酸序列的LCDR1，SEQ ID NO:15所示氨基酸序列的LCDR2，和SEQ ID NO:16所示氨基酸序列的LCDR3；
    优选地，所述化疗药物为铂类抗肿瘤药物和/或紫杉烷类抗肿瘤药物；
    可选地，所述铂类抗肿瘤药物选自顺铂、卡铂、奈达铂、双环铂、吡铂、奥沙利铂、米铂、洛铂、乐铂、四硝酸三铂、菲铂和沙铂中的一种或多种；
    可选地，所述紫杉烷类抗肿瘤药物选自紫杉醇、卡巴他赛和多西他赛中的一种或多种；
    可选地，所述化疗药物为顺铂和紫杉醇，或者，所述化疗药物为卡铂和紫杉醇。
  11. 根据权利要求8-10任一项所述的用途，其中，所述抗TIM-3抗体或其抗原结合片段和抗PD-1抗体或其抗原结合片段，可同时、先后和/或交替给药；或者所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、顺铂和紫杉醇，可同时、先后和/或交替给药；或者所述抗TIM-3抗体或其抗原结合片段、抗PD-1抗体或其抗原结合片段、卡铂和紫杉醇，可同时、先后和/或交替给药。
  12. 根据权利要求8-11任一项所述的用途，其中，
    所述抗TIM-3抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗TIM-3抗体或其抗原结合片段每3周施用一次；可选地，所述抗TIM-3抗体或其抗原结合片段每次以100-1800mg、600-1800mg、600-1500mg、或1200-1500mg的剂量施用，优选地，所述抗TIM-3抗体或其抗原结合片段每次以1200mg的剂量施用；和/或
    所述抗PD-1抗体或其抗原结合片段每1周、每2周、每3周、或每4周施用一次，优选地，所述抗PD-1抗体或其抗原结合片段每3周施用一次；可选地，所述抗PD-1抗体或其抗原结合片段每次以10-800mg、50-500mg、或100-200mg的剂量施用，优选地，所述抗PD-1抗体或其抗原结合片段每次以200mg的剂量施用。
  13. 根据权利要求8-12任一项所述的用途，其中，所述肿瘤为头颈癌；优选地，所述肿瘤为头颈鳞状细胞癌；优选地，所述肿瘤为无局部根治性治疗指征的、局部晚期、复发性或转移性的头颈鳞状细胞癌；
    可选地，所述头颈鳞状细胞癌的主体既往未接受过系统治疗以治疗头颈鳞状细胞癌。
  14. 根据权利要求8-12任一项所述的用途，其中，所述肿瘤为食管癌；优选地，所述肿瘤为食管鳞状细胞癌；优选地，所述肿瘤为不可切除、局部晚期、复发性或转移性的食管鳞状细胞癌；
    可选地，所述食管鳞状细胞癌的主体既往未接受过系统治疗以治疗食管鳞状细胞癌。
  15. 根据权利要求1-7任一项所述的药物组合，或权利要求8-13任一项所述的用途，其中，
    所述抗TIM-3抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:7所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:8所示氨基酸序列具有至少95％同一性的轻链可变区；氨基酸序列与SEQ ID NO:27所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:28所示氨基酸序列具有至少95％同一性的轻链可变区；
    可选地，所述抗TIM-3抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:9所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:10所示氨基酸序列具有至少95％同一性的轻链；
    或氨基酸序列与SEQ ID NO:29所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:30所示氨基酸序列具有至少95％同一性的轻链；
    可选地，所述抗PD-1抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:17所示氨基酸序列具有至少95％同一性的重链可变区，和氨基酸序列与SEQ ID NO:18所示氨基酸序列具有至少95％同一性的轻链可变区；
    可选地，所述抗PD-1抗体或其抗原结合片段包含：氨基酸序列与SEQ ID NO:19所示氨基酸序列具有至少95％同一性的重链，和氨基酸序列与SEQ ID NO:20所示氨基酸序列具有至少95％同一性的轻链。
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