WO2024155790A2

WO2024155790A2 - Novel approach for treatment of cancer using immunomodulation

Info

Publication number: WO2024155790A2
Application number: PCT/US2024/011980
Authority: WO
Inventors: Vincent J. O'NEILL
Original assignee: Onkosxcel Therapeutics, Llc
Priority date: 2023-01-18
Filing date: 2024-01-18
Publication date: 2024-07-25
Also published as: WO2024155790A3

Abstract

The present disclosure provides a regimen for treating a subject afflicted with small cell lung cancer (SCLC) cancer by administering Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists (in particular, PD-L1 antagonist). It further a regimen for treating a subject afflicted with pancreatic cancer by administering Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists (in particular, PD-1 antagonist).

Description

Attorney Reference: ONKO-003/01WO NOVEL APPROACH FOR TREATMENT OF CANCER USING IMMUNOMODULATION CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims priority to from U.S. Provisional Application No. 63/439,752 filed January 18, 2023, the disclosure of which is incorporated by reference herein in its entirety. FIELD [0002] The present disclosure is in the field of immune-oncology, and more specifically relates to a treatment regimen comprising talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists to treat small cell lung cancer (SCLC). It further relates to a treatment regimen comprising talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists to treat pancreatic cancer. BACKGROUND [0003] Cancer is a multistep process that begins with minor pre-neoplastic changes, which may progress to neoplasia, the neoplastic lesions possibly developing an increasing capacity for invasion, growth, metastasis, and heterogeneity. Current therapies for the treatment of cancer involve surgery, hormonal therapy, radiation therapy, chemotherapy and immunotherapy. Immunotherapy for the treatment of cancer has evolved alongside our improved understanding of the immune system. In particular, an appreciation of the ability of cancer cells to subvert the antitumor immune response has provided a rationale for the development of novel immunotherapies that target immune checkpoints responsible for tumor cells escaping detection and destruction by the immune system. [0004] Such immune escape mechanisms are mediated either directly by the tumor cells or by the tumor microenvironment. Tumor cells are known to express membrane proteins, secreted products, enzymes, anti-inflammatory cytokines, and chemokines to produce changes in their genome that aid in immune evasion and immune inhibition. At the same time, a key role is played by the tumor microenvironment. Attorney Reference: ONKO-003/01WO [0005] Immune checkpoint molecules such as PD-1, PD-L1, CTLA-4 are cell surface signaling receptors that play important roles in modulating the T-cell response in the tumor microenvironment. Tumor cells have been shown to utilize these checkpoints to their benefit by up-regulating their expression and activity. Therefore, immune checkpoint inhibitors have been developed which can unleash the immune system’s cancer-destroying properties. Recent discoveries have identified immune checkpoints or targets like PD-1, PD-L1, PD-L2, CTLA4, TIM3, LAG3, CCR4, OX40, OX40L, IDO, and A2AR as proteins responsible for immune evasion, acting as “brakes” of the immune system. Specific immune checkpoint inhibitors, including antibodies against CTLA-4, the PD-1 receptor and its ligand PD-L1 have produced impressive results in the clinic, leading to FDA approvals for Yervoy® (ipilimumab; CTLA-4 antagonist), Opdivo® (nivolumab; PD-1 antagonist) and Tecentriq® (atezolizumab; PD-L1 antagonist) in multiple tumor indications and with on-going clinical trials in many more. [0006] Unfortunately, checkpoint inhibitors suffer from several limitations. Only a minority of patients treated with checkpoint inhibitors exhibit robust anti-tumor responses, and most responses are partial and temporary. Often patients initially respond, but then relapse due to the emergence of resistant pathways, which mainly occur due to the generation by the tumor cells of a non-immune permissive microenvironment. [0007] The combination of the two checkpoint inhibitors, Ipilimumab and Nivolumab, have shown an increase in the response rate in melanoma patients from 11% and 32% seen with the respective monotherapy to 60% with the combination. Unfortunately, this combination has the significant drawback of high toxicity related to an excessive immune response, leading to pneumonitis, hepatitis, colitis and other immune related disorders. [0008] Talabostat also known as PT-100 (Val-boroPro; L-valinyl-L-boroproline), was originally developed by Point Therapeutics, during 2000 to 2007. It is an orally available synthetic selective inhibitor of dipeptidyl peptidases like FAP and DPP8 and DPP9. The stereoisomer of the talabostat molecule disclosed in the U.S. Patent No. 6,825,169 while its oral formulation such as tablet, capsule, lozenges is disclosed in the U.S. Patent No.7,265,118. [0009] Talabostat plays an important role in immune evasion and regulates both innate and/or acquired immunity. However, talabostat has been reported to exhibit a number of side effects at Attorney Reference: ONKO-003/01WO therapeutically effective doses, with the most common adverse events being edema/peripheral swelling, hypotension, hypovolemia, and dizziness. These reported adverse events, as well as insufficient primary and secondary outcomes in certain cancer clinical trials, have led to the limited use of talabostat as an anti-cancer agent. [0010] In our U.S. Patent Application Publication No.2017/0266280A1 (incorporated herein by reference in its entirety), we disclose the novel discovery that the combination of a selective dipeptidyl peptidase (DPP) inhibitor such as talabostat with an immune checkpoint inhibitor is effective in treating cancer. [0011] Surprisingly, the combination is effective without concomitant treatment-limiting side effects. The present disclosure is based on the discovery that talabostat may be particularly effective in treating small cell lung cancer (SCLC) cancer in combination with PD-1 axis antagonist, in particular PD-L1 antagonist) when both are administered at a particular treatment regimen. Further, the present disclosure is based on the discovery that talabostat may be particularly effective in treating pancreatic cancer in combination with PD-1 axis antagonist, in particular, PD-1 antagonist when both are administered at a particular treatment regimen. [0012] Accordingly, the main object of the present disclosure is to provide improved therapies for treating small cell lung cancer (SCLC) using a novel treatment regimen comprising talabostat or a pharmaceutically acceptable salt thereof and a PD-L1 antagonist (for example atezolizumab). Another main object of the present disclosure is treating pancreatic cancer using a novel treatment regimen comprising talabostat or a pharmaceutically acceptable salt thereof and a PD-1 antagonist (for example Pembrolizumab). SUMMARY [0013] The present disclosure is based on the discovery that the combination of talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists (in a specific treatment regimen is a very effective therapy to treat subjects afflicted with small cell lung cancer (SCLC) In particular, the dosage amount of each active used and the dosing schedule selected leads to a very effective treatment of small cell lung cancer (SCLC). In embodiments, the PD-1 axis Attorney Reference: ONKO-003/01WO antagonists include PD1 antagonist (for example anti-PD-1 antibody), PD-Ll antagonist (for example anti-PD-Ll antibody) and PD-L2 antagonist (for example anti-PD-L2 antibody). [0014] In embodiments, the PD-1 axis antagonist is PD-1 antagonist. In embodiments, the PD-1 antagonist is selected from the group consisting of BGB-A317 (i.e., tislelizumab), pembrolizumab, MEDI0680, nivolumab, PDR001 (i.e., spartalizumab), PF-06801591 (i.e., sasanlimab), REGN-2810 (i.e., cemiplimab), SHR-1210 (i.e., camrelizumab), TSR-042 (i.e., dostarlimab), and combination thereof. In embodiments, the PD-1 antagonist is selected from nivolumab or pembrolizumab. [0015] In embodiments, the PD-1 axis antagonist is PD-L1 antagonist. [0016] In embodiments, the present disclosure provides a regimen for treating small cell lung cancer (SCLC) in a subject the treatment regimen comprising administering to the subject, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of a PD-L1 antagonist. In embodiments, the PD-L1 antagonist is selected from the group consisting of avelumab, BMS-936559, CA-170, durvalumab, MCLA-145, SP142, STI-A1011, STI-A1012, STI-A1010, STI-A1014 and atezolizumab and combination thereof. In embodiments, the PD-L1 antagonist is selected from the group consisting of avelumab, durvalumab or atezolizumab. In embodiments, the PD-L1 antagonist is atezolizumab. [0017] In embodiments, the present disclosure provides a regimen for treating small cell lung cancer (SCLC) in a subject , the treatment regimen comprising administering to the subject, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of atezolizumab. [0018] In embodiments, the treatment regimen or the method for treating small cell lung cancer (SCLC) in the subject comprising administering to the subject talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle, and atezolizumab on day 1 of a treatment cycle. [0019] In embodiments, the present disclosure provides a method of treating small cell lung cancer (SCLC), the method comprising administering to a subject an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of atezolizumab. In Attorney Reference: ONKO-003/01WO embodiments, the method comprises at least one administration cycle (e.g. 1, 2, 3, 4, 5, 6 or more cycles), and each treatment cycle is of about 21 days. In embodiments, the treatment is administered for at least 12 weeks, or at least 24 weeks. In embodiments, the patient achieves a complete response within 2-4 weeks after treatment. [0020] In embodiments, there is provided a method of enhancing an immune response in a subject suffering from small cell lung cancer (SCLC), the method comprising administering to the subject a regimen comprising, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of a PD-L1 antagonist. [0021] In embodiments, there is provided a method of enhancing an immune response in a subject suffering from small cell lung cancer (SCLC), the method comprising administering to the subject a regimen comprising, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of atezolizumab. [0022] In embodiments , the present disclosure provides a first pharmaceutical formulation comprising talabostat or a pharmaceutically acceptable salt thereof for use in combination with a separate second pharmaceutical formulation of atezolizumab to treat small cell lung cancer (SCLC), wherein the first pharmaceutical formulation comprises talabostat or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers or adjuvants and the second pharmaceutical formulation comprises atezolizumab together with one or more pharmaceutically acceptable carriers or adjuvants. [0023] In embodiments, the small cell lung cancer (SCLC) is metastatic. In embodiments, the small cell lung cancer is small cell carcinoma. In embodiments, the small cell lung cancer (SCLC) is combined small cell carcinoma. In embodiments, the small cell lung cancer is at an advanced stage. In embodiments, the small cell lung cancer (SCLC) is extensive stage SCLC. [0024] In embodiments the separate pharmaceutical formulations of talabostat or a pharmaceutically acceptable salt thereof and atezolizumab are administered to the subject at relevant times, and in suitable amounts, during one or more treatment cycles of about 21 days, to maximize their combined immunotherapeutic effect. In embodiments, Talabostat or a pharmaceutically acceptable salt thereof is administered at a dose of 0.2 mg twice daily on day 1- Attorney Reference: ONKO-003/01WO 14 of each treatment cycle. In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered at a dose of 0.3 mg twice daily on Day 1-14 of each treatment cycle. [0025] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally (e.g. as a tablet formulation) at a dose of 0.3 mg twice a day. In embodiments, atezolizumab is administered intravenously at a total dose of about 1200 mg as an intravenous infusion over 60 minutes every 3 weeks. [0026] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally at a dose of about 0.2 mg twice daily on day 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on day 8-14 of the first treatment cycle. [0027] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally at a dose of about 0.3 mg twice daily on day 1-3 of the first treatment cycle followed by rest period of 4 days then about 0.3 mg twice daily on day 8-11 of the first treatment cycle. [0028] In embodiments, the subject is not previously treated with PD-1/PD-L1 or CTLA-4 antibodies (or treatment naïve). [0029] In embodiments, the subject has relapsed with PD-1/PD-L1 or CTLA-4 antibodies (or treatment experienced). [0030] In embodiments, the subject has progressed with PD-1/PD-L1 or CTLA-4 antibodies. [0031] In embodiments , the present disclosure provides a method of enhancing an innate immune response in a subject afflicted with small cell lung cancer (SCLC) , the method comprising administering to the subject, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of atezolizumab, wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0032] In embodiments, the present disclosure provides a method of enhancing an innate immune response in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject, an effective amount of talabostat or a pharmaceutically acceptable Attorney Reference: ONKO-003/01WO salt thereof and an effective amount of atezolizumab, wherein the enhanced innate immune response is associated with suppression of T-regulatory cells. [0033] In embodiments, the present disclosure provides a method of enhancing proinflammatory cytokine release in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject, talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and atezolizumab on day 1 of the treatment cycle, wherein the enhanced proinflammatory cytokine release is associated with activation of Natural Killer (NK) cells and T cells resulting in increased antitumor response. [0034] In embodiments, the proinflammatory cytokines are one or more of IL-18, IL-^ȕ^DQG^ ,)1^Ȗ^^ ^ ,Q^ HPERdiments, the subject experiences an increase in pro-inflammatory cytokines relative to a subject. In embodiments, a time -dependent increase in IL-18 levels with maximum increase on day 14 of continuous dosing is observed. [0035] In embodiments, the present disclosure provides a method of reducing the treatment related adverse effects (TRAEs) in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject, talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on one or more days and atezolizumab on day 1 of a treatment cycle. In embodiments, the subject experiences lesser treatment-related adverse events (TRAEs) or (no DLT) relative to a subject with same cancer that is administered a single 0.6 mg once daily dose of talabostat. [0036] In embodiments, the TRAEs are selected from one or more of hypotension, dizziness, headache, syncope, dyspnea, chills, pyrexia, malaise, weakness, edema/peripheral swelling, hypovolemia, hypothermia, fatigue, nausea, vomiting, diaphoresis, flushing, migraine, diarrhea, constipation, alopecia, pharyngitis, chest pain, anorexia, weight increase, weight decrease, vertigo, syncope, conjunctivitis, blurred vision, pallor, pruritus, rash, fungal vaginosis, hyperglycemia, hyperkalemia, hypokalemia, hoarseness, dyspnea, anoxia, deep venous thrombosis, upper respiratory infection, blood in stool, dizziness, rigors, sepsis, pain, hypereosinophilia, dehydration, electrolyte imbalance, arthralgia, rhabdomyolysis, myalgia, constipation, hypocalcemia, neutropenia, febrile neutropenia, anemia, leukopenia, pancytopenia, and lymphopenia, Attorney Reference: ONKO-003/01WO somnolence, insomnia, epistaxis, dyspepsia, dysgeusia, thrombocytopenia, cyanosis peripheral, hypovolemic shock, respiratory failure, cough, pneumonitis, cardiac tamponade, acidosis, renal failure and cardiac arrest. In embodiments, the subject experiences no TRAEs. In embodiments, the subject experiences TRAEs that are consistent with cytokine release. [0037] In embodiments, the present disclosure provides a kit for use in the treatment of small cell lung cancer (SCLC), the kit comprising: (i) a first pharmaceutical formulation comprising talabostat or a pharmaceutically acceptable salt thereof; (ii) a second pharmaceutical formulation comprising atezolizumab; and instructions for using the first and the second pharmaceutical formulations according to the methods and the regimen described herein. [0038] The present disclosure is based on the discovery that the combination of talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist in a specific treatment regimen is a very effective therapy to treat subjects afflicted with pancreatic cancer. In particular, the dosage amount of each active used and the dosing schedule selected leads to a very effective treatment of pancreatic cancer. In embodiments, the PD-1 axis antagonists include PD1 antagonist, PD-Ll antagonist, and PD-L2 antagonist. [0039] In embodiments, the PD-1 axis antagonist is PD1 antagonist. In embodiments, the PD- 1 antagonist is selected from the group consisting of BGB-A317, pembrolizumab, MEDI0680, nivolumab, PDR001, PF-06801591, REGN-2810, SHR-1210, TSR-042, and combination thereof. In embodiments, the PD-1 antagonist is selected from nivolumab or pembrolizumab. [0040] In embodiments, the PD1 antagonist is pembrolizumab. [0041] In embodiments, there is provided a method of enhancing an immune response in a subject suffering from pancreatic cancer, the method comprising administering to the subject a regimen comprising an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of pembrolizumab. Attorney Reference: ONKO-003/01WO [0042] In embodiments , the present disclosure provides a first pharmaceutical formulation comprising talabostat or a pharmaceutically acceptable salt thereof for use in combination with a separate second pharmaceutical formulation of pembrolizumab to treat pancreatic cancer, wherein the first pharmaceutical formulation comprises talabostat or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers or adjuvants and the second pharmaceutical formulation comprises pembrolizumab together with one or more pharmaceutically acceptable carriers or adjuvants. [0043] In embodiments, the pancreatic cancer is metastatic. In embodiments, the pancreatic cancer is neuroendocrine tumor. In embodiments, the pancreatic cancer is pancreatic ductal carcinoma cancer. In embodiments, the pancreatic cancer is at an advanced stage. In embodiments, the pancreatic cancer is extensive stage pancreatic cancer. [0044] In embodiments the separate pharmaceutical formulations of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab are administered to the subject at relevant times, and in suitable amounts, during one or more treatment cycles of about 21 days, to maximize their combined immunotherapeutic effect. In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered at a dose of 0.2 mg twice daily on day 1- 14 of each treatment cycle. In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered at a dose of 0.3 mg twice daily on Day 1-14 of each treatment cycle. [0045] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally (e.g. as a tablet formulation) at a dose of 0.3 mg twice a day. In embodiments, atezolizumab is administered intravenously at a total dose of about 1200 mg as an intravenous infusion over 30 minutes every 3 weeks. [0046] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally at a dose of about 0.2 mg twice daily on day 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on day 8-14 of the first treatment cycle. [0047] In embodiments, talabostat or a pharmaceutically acceptable salt thereof is administered orally at a dose of about 0.3 mg twice daily on day 1-3 of the first treatment cycle Attorney Reference: ONKO-003/01WO followed by rest period of 4 days then about 0.3 mg twice daily on day 8-11 of the first treatment cycle. [0048] In embodiments, the subject is not previously treated with PD-1/PD-L1 or CTLA-4 antibodies (or treatment naïve). [0049] In embodiments, the subject has relapsed with PD-1/PD-L1 or CTLA-4 antibodies (or treatment experienced). [0050] In embodiments, the subject has progressed with PD-1/PD-L1 or CTLA-4 antibodies. [0051] In embodiments, the present disclosure provides a method of enhancing an innate immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of pembrolizumab, wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0052] In embodiments, the present disclosure provides a method of enhancing an innate immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of pembrolizumab, wherein the enhanced innate immune response is associated with suppression of T-regulatory cells. [0053] In embodiments, the present disclosure provides a method of enhancing proinflammatory cytokine release in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and pembrolizumab on day 1 of the treatment cycle, wherein the enhanced proinflammatory cytokine release is associated with activation of NK cells and T cells resulting in increased antitumor response. [0054] In embodiments, the proinflammatory cytokines are one or more of IL-18, IL-^ȕ^DQG^ ,)1^Ȗ^^ ^ ,Q^ HPERGLPHQWV^^ WKH^ VXEMHFW^ H[SHULHQFHV^ DQ^ LQFUHDVH^ LQ^ SUR-inflammatory cytokines relative to a subject. Attorney Reference: ONKO-003/01WO [0055] In embodiments, the present disclosure provides a method of reducing the treatment related adverse effects (TRAEs) in a subject afflicted with pancreatic cancer, comprising administering to the subject, talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on one or more days and pembrolizumab on day 1 of a treatment cycle. In embodiments, the subject experiences lesser treatment-related adverse events (TRAEs) or (no DLT) relative to a subject with same cancer that is administered a single 0.6 mg once daily dose of Talabostat. [0056] In embodiments, the present disclosure provides a method of reducing the treatment related adverse effects (TRAEs) in a subject afflicted with pancreatic cancer, comprising administering to the subject, talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily on one or more days and pembrolizumab on day 1 of a treatment cycle. In embodiments, the subject experiences lesser treatment-related adverse events (TRAEs) or (no DLT) relative to a subject with same cancer that is administered a single 0.4 mg once daily dose of Talabostat. [0057] In embodiments, the TRAEs are selected from one or more of hypotension, dizziness, headache, syncope, dyspnea, chills, pyrexia, malaise, weakness, edema/peripheral swelling, hypovolemia, hypothermia, fatigue, nausea, vomiting, diaphoresis, flushing, migraine, diarrhea, constipation, alopecia, pharyngitis, chest pain, anorexia, weight increase, weight decrease, vertigo, syncope, conjunctivitis, blurred vision, pallor, pruritus, rash, fungal vaginosis, hyperglycemia, hyperkalemia, hypokalemia, hoarseness, dyspnea, anoxia, deep venous thrombosis, upper respiratory infection, blood in stool, dizziness, rigors, sepsis, pain, hypereosinophilia, dehydration, electrolyte imbalance, arthralgia, rhabdomyolysis, myalgia, constipation, hypocalcemia, neutropenia, febrile neutropenia, anemia, leukopenia, pancytopenia, and lymphopenia, somnolence, insomnia, epistaxis, dyspepsia, dysgeusia, thrombocytopenia, cyanosis peripheral, hypovolemic shock, respiratory failure, cough, pneumonitis, cardiac tamponade, acidosis, renal failure and cardiac arrest. In embodiments, the subject experiences no TRAEs. In embodiments, the subject experiences TRAEs that are consistent with cytokine release. [0058] In embodiments, the present disclosure provides a kit for use in the treatment of pancreatic use, the kit comprising: Attorney Reference: ONKO-003/01WO a first pharmaceutical formulation comprising talabostat or a pharmaceutically acceptable salt thereof; a second pharmaceutical formulation comprising pembrolizumab and instructions for using the first and the second pharmaceutical formulations according to the methods and the regimen described herein. [0059] Other features, objects, and advantages of the disclosure will be apparent from the description and drawings, and from the claims. Brief Description of the Drawings: [0060] Figure 1: shows the scheme for administering Talabostat mesylate and Atezolizumab to subjects with SCLC during the treatment Lead-in Stage and the Efficacy Stage. [0061] Figure 2: shows the scheme for administering Talabostat mesylate and Pembrolizumab to subjects with Pancreatic cancer during the treatment Stage. Detailed Description: [0062] In the following passages, different aspects of the disclosure are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous. Abbreviations: [0063] As used herein, the following abbreviations have the following meanings: A2AR: A2A adenosine receptor ALK: Anaplastic lymphoma kinase ALT: Alanine aminotransferase ANC: Absolute neutrophil count Attorney Reference: ONKO-003/01WO AR: Androgen receptor AST: Aspartate aminotransferase AUC: Area under the plasma concentration-time curve AUC _0-last: Area under the plasma concentration time curve for the last measurable concentration BS: Bone scintigraphy BUN: Blood urea nitrogen CAF: Cancer associated fibroblast CR: Complete response CT: Computed tomography CTC: Circulating tumor cells ctDNA: Circulating tumor DNA CTLA4: Cytotoxic T-lymphocyte associated protein 4 CPS: Combined positive scores DPP: Dipeptidyl peptidase DKA: Diabetic ketoacidosis DLT: Dose limiting toxicity DOR: Duration of response DSRC: Data Safety Review Committee EGFR: Epidermal growth factor receptor ECOG: Eastern Cooperative Oncology Group Attorney Reference: ONKO-003/01WO eCRF: Electronic case report form EOT: End of Treatment ES-SCLC: extensive stage small cell lung cancer FAP: Fibroblast activation protein GM-CSF: Granulocyte-macrophage colony-stimulating factor G-CSF: Granulocyte-colony stimulating factor GCP: Good Clinical Practice ICI: Immune check point inhibitor IC50: Half maximal inhibitory concentration ICH: International Council for Harmonisation IEC: Independent Ethics Committee IL: Interleukin IDO: Indoleamine 2,3-dioxygenase IMT : Inflammatory myofibroblastic tumor IPMN: intraductal papillary-mucinous neoplasm IrCR: Immune-related complete disease irPR: Immune-related partial response irSD : Immune-related stable disease IND: Investigational New Drug (Application) IRB: Institutional Review Board Attorney Reference: ONKO-003/01WO iRECIST: Immune Response Evaluation Criteria In Solid tumors ITT: Intent-to-Treat LAG3: Lymphocyte activation gene 3 protein LDH: Lactate dehydrogenase LHRH: Luteinizing hormone-releasing hormone MedDRA: Medical Dictionary for Regulatory Activities MRI: Magnetic resonance imaging mRNA: Messenger ribonucleic acid NK: Natural killer NCI CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events OS: Overall survival PD: Progressive disease PD -1: Programmed cell death 1 PD L1: Programmed death ligand 1 PD L2: Programmed death ligand 2 PFS: Progression-free survival PR: Partial response PD-1: Programmed Cell Death 1 Q.D: Quaque die QTcB: QT interval corrected for heart rate using Bazett’s formula Attorney Reference: ONKO-003/01WO RECIST: Response Evaluation Criteria In Solid Tumors rPFS: Radiographic progression-free survival SD: Stable disease SAE: Serious adverse event SAP: Statistical Analysis Plan SJS: Stevens-Johnson syndrome SCLC: Small cell lung cancer sHASEGP: Soluble neutral-active hyaluronidase glycoproteins TIM3: T-cell immunoglobulin and mucin-domain containing-3 Treg: Regulatory T cells or T-regulatory cells TPS: Tumor Proportion Score TRAE: Treatment related adverse events TEN: Toxic epidermal necrolysis T1DM: Type 1 diabetes mellitus Tmax: Time of maximum observed concentration ULN: Upper limit of normal Definitions: [0064] It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise. [0065] The term "about" as used herein indicates values that may deviate up to 1%, more specifically 5%, more specifically 10%, more specifically 15%, and in some cases up to 20% Attorney Reference: ONKO-003/01WO higher or lower than the value referred to, the deviation range including integer values, and, if applicable, non-integer values as well, constituting a continuous range. As used herein the term "about" refers to ± 10 %. [0066] The terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to". This term encompasses the terms "consisting of" and "consisting essentially of". The phrase "consisting essentially of" means that the composition or method may include additional ingredients and/or steps, but only if the additional ingredients and/or steps do not materially alter the basic and novel characteristics of the claimed composition or method. Throughout this specification and the Examples and claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. [0067] As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts. [0068] As used herein, unless indicated otherwise, the terms “dosage form” "pharmaceutical composition", "composition", "formulation" and "composition of the disclosure," are used interchangeably. [0069] As used herein, the term “effective amount” refers to an amount (quantity or concentration) sufficient to produce the desired effect (i.e. prevent, alleviate, or ameliorate symptoms of disease or condition or prolong the survival of the subject being treated) or cause an improvement in a clinically significant condition of the subject. The effective amount will depend on the particular disorder, the mode of administration, co-administered compounds, if any, and the characteristics of the subject, such as general health, other diseases, age, sex, genotype, body weight, and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors Attorney Reference: ONKO-003/01WO [0070] As used herein, the terms “subject” or “patient” are used interchangeably and refers to human subjects in need of treatment for SCLC or pancreatic cancer. [0071] As used herein, "pharmaceutically acceptable salt" refers to a salt known to be non- toxic and commonly used in the pharmaceutical literature. Typical inorganic acids used to form such salts hydrochloric, hydrobromic, hydroiodic, nitric, sulfuric, phosphoric, hypophosphoric, and the like, as well as those prepared from organic acids, such as for example, aliphatic mono and dicarboxylic acids, phenyl substituted alkanoic acids, hydroxyalkanoic and hydroxyl alkandioic acids, aromatic acids, aliphatic (mesylate) and aromatic sulfonic acids. A preferred salt form of Talabostat is the mesylate salt. [0072] As used herein, the terms, “administering” or “administration of” a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art. For example, a compound or an agent can be administered orally, buccally, parenterally, intravenously, intramuscularly, subcutaneously, inhalationally, intranasally, transdermally, rectally, or vaginally. The administration can also be performed, for example, once, or a plurality of times per day, and/or over one or more longer periods. In embodiments, the administration includes both direct administrations, including self-administration, and indirect administration, including the act of prescribing a drug. For example, as used herein, administration via a physician or a physician who instructs a patient to self-administer a drug, or to have the drug administered by another and/or who provides a patient with a prescription for a drug is administering the drug to the patient. [0073] As used herein, the term, “treat” and its cognates refers to taking steps to obtain beneficial or desired results, i.e., to obtain a full or partial amelioration of SCLC or pancreatic cancer. [0074] As used herein, the term “treatment naïve” includes patient/subject who is considered ineligible for standard induction chemotherapy. [0075] The term "pharmaceutically acceptable carrier" refers to a pharmacologically inert substance to be used as a carrier. As used herein, the phrase “carrier” and “excipients” are used interchangeably, except where otherwise clearly intended to have different meanings. Attorney Reference: ONKO-003/01WO [0076] The term “measurable disease” as used herein refers to presence of at least one measurable lesion. Measurable lesions must be accurately measured in at least 1 dimension (longest diameter in the plane of the measurement to be recorded) with a minimum size of: x 10 mm by CT scan (CT scan slice thickness no greater than 5 mm). x 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable). x 20 mm by chest X-ray. [0077] The term “malignant lymph nodes” is defined to be pathologically enlarged and PHDVXUDEOH^^LI^D^O\PSK^QRGH^ZDV^^^^^PP^LQ^VKRUW^D[LV^ZKHQ^DVVHVVHG^E\^&7^VFDQ^^&7^VFDQ^VOLFH^ thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis was measured and followed. [0078] Non-measurable lesions were all other lesions, including small lesions (longest GLDPHWHU^^^^^PP^RU^SDWKRORJLFDO^O\PSK^QRGHV^ZLWK^^^^^WR^^^^^PP^VKRUW^D[LV^^^DV^ZHOO^DV^QRQ- measurable lesions. [0079] The term “target lesions” refers to when more than one lesion is present at baseline all lesions up to a maximum of five lesions total representative of all involved organs are identified as target lesions. All other lesions including pathological lymph nodes are identified as “non-target lesions” and are also recorded at baseline. [0080] The term “complete response” or (CR) as used herein refers to disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non- pathological in size (<10mm short axis). [0081] The term “non-CR/non-PD” as used herein refers to persistence of one or more non- target lesion(s) and/or maintenance of tumor marker level above the normal limits. The term “progressive disease” as used herein refers to unequivocal progression of existing non-target lesions. Attorney Reference: ONKO-003/01WO [0082] The term “unequivocal progression” as used herein refers to an overall level of substantial worsening in non-target disease such that even in presence of SD or PR in target disease, the overall burden had increased sufficiently to merit discontinuation of therapy. [0083] The term “not evaluable or NE” or “unevaluable” refers to when no imaging/measurement is done at all at a particular time point. [0084] Radiographic PFS is defined as the time from the date of initiation of protocol therapy to date measurement criteria were first met for PD by RECIST 1.1 or death from any cause, whichever occurred first. [0085] Progression Free Survival (PFS) is defined as the time from the date of initiation of protocol therapy to date measurement criteria were first met for tumor progression. [0086] Overall Survival: Survival time was the difference in days between the date of death and the first date of study treatment (+1 day). Therapeutic agents [0087] The therapeutic agents talabostat and atezolizumab as intended for use in the present disclosure are described below: a) Talabostat or a pharmaceutically acceptable salt thereof: [0088] Talabostat is referred to interchangeably as PT-100, Talabostat (USAN), and [(2R)-I- I [(2S)-2-amino-3-methyl-1-oxobutyl]-2-pyrrolidinyl] boronic acid. Talabostat has a CAS registration number of 149682- 77-9. Talabostat, also known as Val-boro-pro (L-valinyl-L- boroproline), is disclosed in PCT Appl. Publication No. 1989/003223. The IUPAC name of talabostat is [(2R)-1-[(2S)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid. Talabostat (PubChem ID: 6918572), or a pharmaceutically acceptable salt thereof, such as, for example, talabostat mesylate (PubChem CID: 1152248). In embodiments, the free base may be used. In embodiments, the talabostat or a pharmaceutically acceptable salt thereof may be a solvate. In most clinical formulations, talabostat is provided as a salt form, e.g. talabostat mesylate. Talabostat has two chiral centers with a R, S configuration. Talabostat or a pharmaceutically acceptable salt Attorney Reference: ONKO-003/01WO thereof can exist as both linear and cyclic forms (RJ Snow et al., J. Am. Chem. Soc., 1994, 116 (24), pp 10860–10869). [0089] Talabostat or a pharmaceutically acceptable salt thereof is effective for the treatment of cancer by modulating multiple intracellular and extracellular dipeptidyl peptidases. More specifically, intracellular and extracellular dipeptidyl peptidases comprise Fibroblast Activation Protein, DPP 8/9, CD26/DPP4 and DPP2. Talabostat or a pharmaceutically acceptable salt thereof has a dual mechanism of action which includes stromal targeted activity via FAP inhibition and targeted immunostimulatory activity via DPP 8/9 inhibition. Talabostat inhibits FAP enzymatic activity thereby suppressing tumor growth. Talabostat or a pharmaceutically acceptable salt WKHUHRI^DOVR^LQKLELWV^'33^^^^WKHUHE\^LQGXFLQJ^DQ^,/^^ȕ^UHVSRQVH^^YLD^FDVSDVH-1) in the stroma of tumor and lymph nodes. Talabostat’s dual mechanism of action introduces a novel approach to the treatment of cancer because it combines both tumor-targeted and immune-stimulatory activity in a single agent. [0090] In embodiments, Talabostat or a pharmaceutically acceptable salt thereof is Talabostat mesylate. b) Atezolizumab: [0091] Atezolizumab is an Fc-engineered, humanized, monoclonal antibody that binds to PD- L1 and blocks interactions with the PD-1 and B7.1 receptors. This releases the PD-L1/PD-1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibody dependent cellular cytotoxicity. Atezolizumab is a non- glycosylated IgG1 kappa immunoglobulin that has a calculated molecular mass of 145 kDa. Atezolizumab may be readily procured from the marketplace and it is available under trade name Tecentriq. [0092] Atezolizumab, also known as MPDL3280A, RG-7446; RG7446-42; RO-5541267 and Tecentriq® (Genentech Oncology, a subsidiary of Roche Group), is disclosed in US patent No. US8217149. It is approved in the United States and the European Union for the treatment of patients with localized advanced or metastatic UC after prior platinum-containing chemotherapy or who are considered cisplatin-ineligible (Rosenberg et al 2016, Loriot et al 2016). Atezolizumab Attorney Reference: ONKO-003/01WO is also approved for patients with locally advanced or metastatic NSCLC after prior chemotherapy (Fehrenbacher et al 2016; Tecentriq US Prescribing Information; EMA SmPC). [0093] c) Pembrolizumab [0094] Pembrolizumab: Pembrolizumab (also known as MK-3475, Lambrolizumab, KEYTRUDA®, and SCH-900475) is a humanized antibody, which targets the PD-1 receptor of lymphocytes, thereby blocking PD-1 inhibitory signal transduction. Pembrolizumab may be readily procured from the marketplace. 1. Methods of use: A) SCLC [0095] The present disclosure is based, in part, on an improved regimen to treat small cell lung cancer ( SCLC) using effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist, in particular PD-L1 antagonist . The combination of Talabostat or a pharmaceutically acceptable salt thereof and PD-L1 antagonist as used herein may produce an overall enhanced anti-cancer effect, such as improved T-cell priming, increased T cell stimulation, increased infiltration of neutrophil and macrophages across tumor microenvironment, decreased tumor volume, increased activation of natural killer cells, enhanced activation of dendritic cells, synergistic increase in pro-inflammatory cytokine (IL1. IL2, IL18, IFN gamma, IL6, IL12p40, IL 15, IL 7, G-CSF and GM-CSF), enhanced anti-tumor memory response, reduced metastasis and reduced toxicity. In embodiments, the PD-L1 antagonist is selected from the group consisting of Avelumab, Durvalumab or Atezolizumab. In embodiments, the PD-L1 antagonist is Atezolizumab. [0096] In embodiments, the present disclosure provides a combination comprising an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab administered to a subject afflicted with small cell lung cancer (SCLC) in one or more treatment cycles, each cycle of about 21 days duration. In embodiments, the small cell lung cancer is ES-SCLC. Attorney Reference: ONKO-003/01WO [0097] An advantage of using the particular regimen of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab of this disclosure is in the curtailment of the progression of small cell lung cancer (SCLC), reduction in tumor burden, reduced metastasis and/or inducement of tumor regression in a subject. [0098] Thus, in one embodiment the present disclosure relates to a combination of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab administered to a subject afflicted with small cell lung cancer in a particular treatment regimen to promote an effective anti-tumor response. [0099] In embodiments, provided herein is a method of delaying progression of or preventing or delaying tumor recurrence, tumor growth or spread of tumor, in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, , effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. [0100] In some embodiments, the present disclosure provides a method of delaying progression of or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with small cell lung cancer (e.g. ES- SCLC), comprising administering Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and the Atezolizumab is administered on day 1 of the treatment cycle. [0101] In embodiment, provided herein is a method of enhancing immune function in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. [0102] In embodiment, provided herein is a method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically Attorney Reference: ONKO-003/01WO acceptable salt thereof and Atezolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. [0103] In embodiments, provided herein is a method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering a therapeutically effective amount of Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and the Atezolizumab is administered on day 1 of the treatment cycle. In embodiments, the treatment regimen described herein results in a sustained response in the subject after cessation of the treatment. [0104] In embodiments, the subject has a small cell lung cancer (SCLC) that may be at an early stage or a late stage. In embodiments, the small cell lung cancer is at extensive stage. [0105] In embodiments, the small cell lung cancer is metastatic. [0106] In embodiments, the subject is a human. [0107] In embodiments, the present disclosure provides a method for reducing the toxicity of Talabostat or a pharmaceutically acceptable salt thereof with a lower effective dose of talabostat, the method comprising administering to a subject afflicted with small cell lung cancer, the talabostat or the pharmaceutically acceptable salt thereof and the atezolizumab in the treatment regimen described herein. In embodiments, the treatment regimen of the present disclosure comprises the use of effective amounts of talabostat or a pharmaceutically acceptable salt thereof and atezolizumab to produce an increased innate immune response as compared to the innate immune response when the subject is administered Talabostat alone. The innate immune response may be increased by infiltration of innate immune cells, in particular macrophages into the blood, and NK-cells into the tumor. Further, the present treatment regimen comprising effective amounts of talabostat or a pharmaceutically acceptable salt thereof and atezolizumab can produce suppression of the Treg function that is greater than that obtained using talabostat alone. Attorney Reference: ONKO-003/01WO [0108] The present treatment regimen comprising effective amounts of talabostat or a pharmaceutically acceptable salt thereof and atezolizumab can also significantly increase the tumor infiltration of immune sub-populations, such as NK-cells and macrophages, compared to monotherapies using talabostat or a pharmaceutically acceptable salt thereof and atezolizumab. B) Pancreatic cancer [0109] The present disclosure is based, in part, on an improved regimen to treat pancreatic cancer using effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD- 1 axis antagonist, in particular PD-1 antagonist. The combination of talabostat or a pharmaceutically acceptable salt thereof and PD-1 antagonist as used herein may produce an overall enhanced anti-cancer effect, such as improved T-cell priming, increased T cell stimulation, increased infiltration of neutrophil and macrophages across tumor microenvironment, decreased tumor volume, increased activation of natural killer cells, enhanced activation of dendritic cells, synergistic increase in pro-inflammatory cytokine (IL1. IL2, IL18, IFN gamma, IL6, IL12p40, IL 15, IL 7, G-CSF and GM-CSF), enhanced anti-tumor memory response, reduced metastasis and reduced toxicity. In embodiments, the PD-1 antagonist is selected from the group consisting of, BGB-A317, Pembrolizumab, MEDI0680, Nivolumab, PDR001, PF-06801591, REGN-2810, SHR-1210, TSR-042, and combination thereof. In embodiments, the PD-1 antagonist is selected from Nivolumab or Pembrolizumab. In embodiments, the PD-1 antagonist is Pembrolizumab. [0110] In embodiments, the present disclosure provides a combination comprising an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of pembrolizumab administered to a subject afflicted with pancreatic cancer in one or more treatment cycles, wherein each cycle is of about 21 days duration. In embodiments, the pancreatic cancer is pancreatic ductal carcinoma. [0111] An advantage of using the particular regimen of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab of this disclosure is in the curtailment of the progression of pancreatic cancer, reduction in tumor burden, reduced metastasis and/or inducement of tumor regression in a subject. Attorney Reference: ONKO-003/01WO [0112] Thus, in one embodiment the present disclosure relates to a combination of talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab administered to a subject afflicted with pancreatic cancer in a particular treatment regimen to promote an effective anti- tumor response. [0113] In embodiments, provided herein is a method of delaying progression of or preventing or delaying tumor recurrence, tumor growth or spread of tumor, in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. [0114] In some embodiments, the present disclosure provides a method of delaying progression of or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with pancreatic cancer (e.g. pancreatic ductal carcinoma), comprising administering talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of pembrolizumab, wherein the talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and the pembrolizumab is administered on day 1 of the treatment cycle. [0115] In some embodiments, the present disclosure provides a method of delaying progression of or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with pancreatic cancer (e.g. pancreatic ductal carcinoma), comprising administering talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of pembrolizumab, wherein the talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.2 mg twice daily on one or more days of a treatment cycle and the pembrolizumab is administered on day 1 of the treatment cycle. [0116] In embodiment, provided herein is a method of enhancing immune function in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. Attorney Reference: ONKO-003/01WO [0117] In embodiment, provided herein is a method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab over one or more treatment cycles, wherein each cycle is of about 21 days duration. [0118] In embodiments, provided herein is a method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with pancreatic cancer, the method comprising administering a therapeutically effective amount of talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of pembrolizumab, wherein the talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and the pembrolizumab is administered on day 1 of the treatment cycle. In embodiments, the treatment regimen described herein results in a sustained response in the subject after cessation of the treatment. [0119] In embodiments, the subject has a pancreatic cancer selected from a group comprising exocrine pancreatic cancer, pancreatic ductal carcinoma or adenocarcinoma of pancreas, squamous cell carcinoma, adeno-squamous carcinoma, colloid carcinoma, pancreatic neuroendocrine tumors, acinar cell carcinoma, intraductal papillary-mucinous neoplasm (IPMN) or mucinous cystic neoplasm with an invasive adenocarcinoma. [0120] In embodiments, the subject has a pancreatic cancer that may be at an early stage or a late stage. In embodiments, the pancreatic cancer is at extensive stage. [0121] In embodiments, the pancreatic cancer is metastatic. [0122] In embodiments, the subject is a human. [0123] In embodiment, the present disclosure provides a method for reducing the toxicity of Talabostat or a pharmaceutically acceptable salt thereof with a lower effective dose of Talabostat, the method comprising administering to a subject afflicted with pancreatic cancer, talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab in the treatment regimen described herein. Attorney Reference: ONKO-003/01WO [0124] In embodiment, the treatment regimen of the present disclosure comprises the use effective amounts of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab to produce an increased innate immune response as compared to the innate immune response when the subject is administered talabostat alone. The innate immune response may be increased by infiltration of innate immune cells, in particular macrophages into the blood, and NK-cells into the tumor. Further, the present treatment regimen comprising effective amounts of talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab can produce suppression of the Treg function that is greater than that obtained using talabostat alone. [0125] The present treatment regimen comprising effective amounts of talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab can also significantly increase the tumor infiltration of immune sub-populations, such as NK-cells and macrophages, compared to monotherapies using talabostat or a pharmaceutically acceptable salt thereof and pembrolizumab. Dosage and Treatment Regimens: A) SCLC [0126] In embodiments, each treatment cycle is from 1 to 30 days in duration. For example, each treatment cycle is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days. In embodiments, each treatment cycle is 21 days in duration. In embodiments, the subject is administered Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists (e.g. PD-1 antagonist, PD-L1 antagonist and PD-L2 antagonist) for one or more treatment cycles. In embodiments, during each treatment cycle of about 21 days, Talabostat or a pharmaceutically acceptable salt thereof may be administered at an effective dose on each of days 1 to 14 and PD-1 axis antagonists (e.g. PD-1 antagonist, PD-L1 antagonist and PD-L2 antagonist) may be administered at an effective dose on day 1. In embodiments, the PD-1 axis antagonist is a PD-L1 antagonist selected from the group consisting of avelumab, BMS- 936559, CA-170, durvalumab, MCLA-145, SP142, STI-A1011, STI-A1012, STI-A1010, STI- A1014 and Atezolizumab and combination thereof. In embodiments, the PD-L1 antagonist is selected from the group consisting of Avelumab, Durvalumab or Atezolizumab. In embodiments, the PD-L1 antagonist is Atezolizumab. Attorney Reference: ONKO-003/01WO [0127] In embodiments, the PD-1 axis antagonist is a PD-1 antagonist selected from the group consisting of BGB-A317, Pembrolizumab, MEDI0680, Nivolumab, PDR001, PF-06801591, REGN-2810, SHR-1210, TSR-042, and combination thereof. [0128] Said regimen is effective to treat a subject afflicted with small cell lung cancer (for e.g. ES-SCLC). [0129] Talabostat or a pharmaceutically acceptable salt thereof may be administered as a single daily dose or, as multiple dosage units to achieve an effective total daily dose to treat a subject afflicted with small cell lung cancer (SCLC). In embodiments, Talabostat or a pharmaceutically acceptable salt thereof may be administered twice a day. In embodiments, Talabostat or a pharmaceutically acceptable salt thereof is administered at a dose 0.2 mg twice a day for a sufficient time (e.g. for 1 to 30 days) followed by 0.3 mg twice a day thereafter. For example, Talabostat or a pharmaceutically acceptable salt thereof is administered at a dose 0.2 mg twice a day for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days, followed by 0.3 mg twice a day thereafter (i.e. for the remainder of the treatment cycle and for each treatment cycle thereafter). [0130] In embodiments, Talabostat or a pharmaceutically acceptable salt thereof is administered at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8-14 of the first treatment cycle. In embodiments, Talabostat or a pharmaceutically acceptable salt thereof may be administered at 0.3 mg as a morning dose (e.g. about 5 am, about 6 am, about 7 am, about 8 am, about 9 am, about 10 am, or about 11 am) and 0.3 mg as an evening dose (e.g. about 5 pm, about 6 pm, about 7 pm, about 8 pm, about 9 pm, about 10 pm, or about 11 pm). [0131] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and Atezolizumab is administered on day 1 of the treatment cycle. [0132] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab are administered according to an intermittent dosing regimen. The term “intermittent dosing regimen” refers to repeating cycles of drug administration in which the drug Attorney Reference: ONKO-003/01WO is administered on one or more consecutive days (“days on”) followed by one or more consecutive days of rest on which the drug is not administered (“days off”). The cycles may be regular, in that the pattern of days on and days off is the same in each cycle, or may be irregular. In embodiments, the cycle is 21 days and the Talabostat or the pharmaceutically acceptable salt thereof is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 consecutive days followed by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days where the patient takes no Talabostat. In embodiments, this intermittent dosing schedule occurs multiple times within the same cycle. For example, in embodiments, the cycle is 21 days and Atezolizumab is administered intravenously on day 1 and Talabostat or a pharmaceutically acceptable salt thereof is administered for 3 consecutive days followed by 4 days where the patient takes no Talabostat, and this 7 day pattern repeats once (i.e. no Talabostat is administered on days 15-21) or twice. In embodiments, Talabostat or a pharmaceutically acceptable salt thereof is administered orally (e.g. by tablet) on each of days 1 to 14 and Atezolizumab is administered intravenously on day 1 and no drug is administered on days 15-21. [0133] Atezolizumab may conveniently be administered as a single dose in the regimen of this disclosure to effectively treat a subject afflicted with small cell lung cancer (SCLC). In embodiments, Atezolizumab is administered intravenously on day 1 where no drug is administered on days 15-21. [0134] In embodiments, Atezolizumab may be administered at a total dose of about 1 mg/kg to about 20 mg/kg per day, conveniently by injection (e.g., intravenously), most preferably as continuous infusion for 60 minutes. A suitable dose of Atezolizumab administered intravenously in the treatment regimen of the present disclosure may conveniently be from about 50 mg to about 1500 mg, about 500 mg to about 1500 mg per day, e.g. about 1200 mg per day every 3 weeks. [0135] In embodiments, the total dose of Atezolizumab administered intravenously in the treatment regimen of the present disclosure may conveniently be from about 50 mg to about 1500 mg, about 60 mg to about 1500 mg, about 70 mg to about 1500 mg, about 80 mg to about 1500 mg, about 90 mg to about 1500 mg, about 100 mg to about 1500 mg, about 150 mg to about 1500 mg, about 200 mg to about 1500 mg, about 250 mg to about 1500 mg, about 300 mg to about 1500 mg, about 350 mg to about 1500 mg, about 400 mg to about 1500 mg, about 450 mg to about 1500 Attorney Reference: ONKO-003/01WO mg, about 500 mg to about 1500 mg, about 600 to about 1500 mg, about 700 mg to about 1500 mg, about 800 mg to about 1500 mg, about 900 mg to about 1500 mg, about 1000 mg to about 1500 mg, about 1100 mg to about 1500 mg, about 1200 mg to about 1500 mg, about 1300 mg to about 1500 mg, or about 1400 mg to about 1500 mg. [0136] In embodiments, Atezolizumab (Tecentriq) is administered as a liquid medicament which comprises 60 mg of Atezolizumab and is formulated in glacial acetic acid (16.5 mg), L- histidine (62 mg), sucrose (821.6 mg), polysorbate 20 (8 mg), pH 5.85, and the selected dose of the medicament is administered by IV infusion over a time period of about 30-60 minutes. [0137] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof (e.g., Talabostat mesylate) may be administered at a total daily dose of about 0.001 mg/kg to about 0.1 mg/kg (e.g. about 0.001 mg/kg to about 0.035 mg/kg, or about 0.001 mg/kg to about 0.014 mg/kg), conveniently by the oral route (e.g. tablet). A suitable daily dose of the talabostat or the pharmaceutically acceptable salt thereof (e.g. talabostat mesylate) administered orally via one or more (e.g. two or three) tablets in the treatment regimen of the present disclosure may conveniently be from about 0.1 mg to about 1 mg (e.g. about 0.05 mg, about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, preferably about 0.1 mg to about 0.6 mg, more preferably about 0.4 mg to about 0.6 mg). In embodiments, the talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) may be administered orally at a dose of about 0.2 mg twice daily in divided doses In embodiments, the talabostat or the pharmaceutically acceptable salt thereof e.g. Talabostat mesylate) may be administered orally at a dose of about 0.3 mg twice daily in divided doses. In embodiment, the Talabostat or the pharmaceutically acceptable salt thereof may be administered orally at a dose of about 0.2 mg thrice daily in divided doses. In embodiment, the Talabostat or the pharmaceutically acceptable salt thereof (e.g., talabostat mesylate) may be administered orally twice daily, such as at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening in a day. [0138] Suitable treatment regimens for treating a human patient afflicted with small cell lung cancer (SCLC) include, for example, administering to the patient, , an effective amount of each of the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab, wherein Attorney Reference: ONKO-003/01WO the regimen comprises at least one administration cycle (e.g. 1, 2, 3, 4, 5, 6 or more cycles), wherein each cycle is a period of about 21 days, and wherein for each cycle, the Talabostat or the pharmaceutically acceptable salt thereof is administered orally (e.g. by tablet) on each of days 1 to 14 and the Atezolizumab is administered intravenously on day 1. [0139] In embodiment, during one or more treatment cycles of about 21 days, the Talabostat or the pharmaceutically acceptable salt thereof (Talabostat mesylate) is administered on days 1 to 14 at a total daily dose of about 0.4 mg to about 0.6 mg and the Atezolizumab is administered on day 1 at a total dose of about 100 mg to about 1500 mg per day, e.g. about 1200 mg per day. [0140] In embodiment, the daily dose of Talabostat or a pharmaceutically acceptable salt thereof may be varied over time. For example, during the first cycle (including the Lead-in Stage) the Talabostat or the pharmaceutically acceptable salt thereof may be administered at a lower daily dose than during subsequent cycles (e.g. Efficacy Stage). For example, the Talabostat or the pharmaceutically acceptable salt thereof may conveniently be administered during the Lead-in Stage a daily dose of about 0.4 mg, and, if there are no side effects or other criteria preventing further treatment, the subject is allowed to enter the Efficacy Stage and administered, during Efficacy Stage, a daily dose of about 0.6 mg (for e.g. administered in split doses as 0.3 mg twice daily). In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof may be administered during the Lead-in Stage a daily dose of about 0.6 mg and during the Efficacy Stage a daily dose of about 0.4 mg. In embodiments, the patient is treated directly in the Efficacy Stage using a daily dose of about 0.4 mg or about 0.6 mg. [0141] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab are administered to a subject afflicted with small cell lung cancer (SCLC) cancer (e.g. SCNC) in any desired number of treatment cycles as long as a clinical benefit is observed or until there is a complete response, confirmed progressive disease or unmanageable toxicity. [0142] In embodiments, the daily dosages of Talabostat or the pharmaceutically acceptable salt thereof (e.g., talabostat mesylate) and the Atezolizumab used according to the treatment regimen of this disclosure may be lower than the daily dosages of one or both of the Talabostat or the pharmaceutically acceptable salt thereof (e.g., talabostat mesylate) and the atezolizumab administered as single agents to treat a subject afflicted with small cell lung cancer (e.g. ES-SCLC) Attorney Reference: ONKO-003/01WO [0143] In embodiments, the combination therapy is preferably administered for at least 12 weeks (three 4-week cycles or four 3-week cycles), more preferably at least 24 weeks (six 4-week cycles or eight 3-week cycles), and even more preferably at least 1 to 4 weeks after the patient achieves a complete response. [0144] In embodiments, a single administration cycle comprises 21 days (21- day cycle). In embodiments, talabostat mesylate is administered once daily (QD) on Days 1 to 14 of a 21-day cycle plus atezolizumab as 1200 mg administered intravenously (IV) on Day 1 every 21 days. [0145] In embodiments, a single administration cycle comprises 21 days (21- day cycle). In embodiment, talabostat mesylate is administered twice daily at a dose of 0.3 mg on Days 1 to 14 of a 21-day cycle plus atezolizumab 1200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, talabostat mesylate is administered thrice daily at a dose of about 0.2 mg on Days 1 to 14 of a 21-day cycle plus atezolizumab 1200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, talabostat mesylate is administered at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening on Days 1 to 14 of a 21-day cycle plus atezolizumab 1200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, talabostat mesylate is administered at a dose of about 0.2 mg in the morning and about 0.4 mg in the evening on Days 1 to 14 of a 21-day cycle plus atezolizumab 1200 mg administered intravenously (IV) on Day 1 every 21 days. [0146] In embodiments, Talabostat mesylate is administered twice daily at a dose of about 0.3 mg on Days 1 to 3 of a 21-day cycle plus Atezolizumab 1200 mg administered intravenously (IV) on Day 1 every 21 days followed by rest period from day 4-7 (no dose of Talabostat given) and then followed by Talabostat mesylate is administered twice daily at a dose of about 0.3 mg on Days 8 to 11 of a 21-day cycle. [0147] In embodiments, the combination therapy of the disclosure is administered to a patient who has not been previously treated with a biotherapeutic or chemotherapeutic agent, i.e., is treatment- naive. In embodiments, the combination therapy is administered to a patient who failed to achieve a sustained response after prior therapy with a biotherapeutic or chemotherapeutic agent, i.e., is treatment- experienced. Attorney Reference: ONKO-003/01WO [0148] In embodiments, the subject is treated with a single daily 0.6 mg dose of Talabostat mesylate and experienced dose-limiting side effects. [0149] In embodiments of any of the methods or the regimen described herein, before the period of time, the subject was treated with Talabostat mesylate as a monotherapy, and, optionally, the prior treatment with the Talabostat mesylate as a monotherapy was unsuccessful. In embodiments of any of the methods or the regimen described herein, before the period of time, the patient was treated with Atezolizumab, or a biosimilar thereof as a monotherapy, and optionally, the prior treatment with Atezolizumab, or a biosimilar thereof was unsuccessful. [0150] A suitable period of time can be determined by one skilled in the art (e.g., a physician). As can be appreciated in the art, a suitable period of time can be determined by one skilled in the art based on one or more of: the stage of disease in the patient, the mass and sex of the patient, clinical trial guidelines (e.g., those on the fda.gov website), and information on the approved drug label. For example a suitable period of time can be, e.g., from 1 week to 2 years, 1 week to 22 months, 1 week to 20 months, 1 week to 18 months, 1 week to 16 months, 1 week to 14 months, 1 week to 12 months, 1 week to 10 months, 1 week to 8 months, 1 week to 6 months, 1 week to 4 months 1 week to 2 months, 1 week to 1 month, 2 weeks to 2 years, 2 weeks to 22 months, 2 weeks to 20 months, 2 weeks to 18 months, 2 weeks to 16 months, 2 weeks to 14 months, 2 weeks to 12 months, 2 weeks to 10 months, 2 weeks to 8 months, 2 weeks to 6 months, 2 weeks to 4 months, 2 weeks to 2 months, 2 weeks to 1 month, 1 month to 2 years, 1 month to 22 months, 1 month to 20 months, 1 month to 18 months, 1 month to 16 months, 1 month to 14 months, 1 month to 12 months, 1 month to 10 months, 1 month to 8 months, 1 month to 6 months, 1 month to 4 months, 1 month to 2 months, 2 months to 2 years, 2 months to 22 months, 2 months to 20 months, 2 months to 18 months, 2 months to 16 months, 2 months to 14 months, 2 months to 12 months, 2 months to 10 months, 2 months to 8 months, 2 months to 6 months, 2 months to 4 months, 3 months to 2 years, 3 months to 22 months, 3 months to 20 months, 3 months to 18 months, 3 months to 16 months, 3 months to 14 months, 3 months to 12 months, 3 months to 10 months, 3 months to 8 months, 3 months to 6 months, 4 months to 2 years, 4 months to 22 months, 4 months to 20 months, 4 months to 18 months, 4 months to 16 months, 4 months to 14 months, 4 months to 12 months, 4 months to 10 months, 4 months to 8 months, 4 months to 6 months, 6 months to 2 years, 6 months to 22 months, 6 months to 20 months, 6 months to 18 months, 6 months to 16 Attorney Reference: ONKO-003/01WO months, 6 months to 14 months, 6 months to 12 months, 6 months to 10 months, 6 months to 8 months, 8 months to 2 years, 8 months to 22 months, 8 months to 20 months, 8 months to 18 months, 8 months to 16 months, 8 months to 14 months, 8 months to 12 months, 8 months to 10 months, 10 months to 2 years, 10 months to 22 months, 10 months to 20 months, 10 months to 18 months, 10 months to 16 months, 10 months to 14 months, 10 months to 12 months, 12 months to 2 years, 12 months to 22 months, 12 months to 20 months, 12 months to 18 months, 12 months to 16 months, or 12 months to 14 months, inclusive. B) Pancreatic cancer [0151] In embodiments, each treatment cycle is from 1 to 30 days in duration. For example, each treatment cycle is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days. In embodiments, each treatment cycle is 21 days in duration. In embodiments, the subject is administered Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonists (e.g. PD-1 antagonist, PD-L1 antagonist and PD-L2 antagonist) for one or more treatment cycles. In embodiments, the PD-1 axis antagonist is PD-1 antagonist (for example anti-PD-1 antibody). In embodiments, the PD-1 antagonist is an anti-PD-1 antibody selected from Nivolumab or Pembrolizumab [0152] In embodiments, the PD-1 antagonist is Pembrolizumab. In embodiments, during each treatment cycle of about 21 days, the Talabostat or the pharmaceutically acceptable salt thereof may be administered at an effective dose on each of days 1 to 14 and Pembrolizumab may be administered at an effective dose on day 1. Said regimen is effective to treat a subject afflicted with pancreatic cancer (for e.g. pancreatic ductal carcinoma). [0153] Talabostat or a pharmaceutically acceptable salt thereof may be administered as a single daily dose or, as multiple dosage units to achieve an effective total daily dose to treat a subject afflicted with pancreatic cancer. In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof may be administered twice a day. In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose 0.2 mg twice a day for a sufficient time (e.g. for 1 to 30 days) followed by 0.3 mg twice a day thereafter. For example, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose 0.2 mg twice Attorney Reference: ONKO-003/01WO a day for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days, followed by 0.3 mg twice a day thereafter (i.e. for the remainder of the treatment cycle and for each treatment cycle thereafter). [0154] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8-14 of the first treatment cycle. In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof may be administered at 0.3 mg as a morning dose (e.g. about 5 am, about 6 am, about 7 am, about 8 am, about 9 am, about 10 am, or about 11 am) and 0.3 mg as an evening dose (e.g. about 5 pm, about 6 pm, about 7 pm, about 8 pm, about 9 pm, about 10 pm, or about 11 pm). [0155] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and the Pembrolizumab is administered on day 1 of the treatment cycle. [0156] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.2 mg twice daily on one or more days of a treatment cycle and the Pembrolizumab is administered on day 1 of the treatment cycle. [0157] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab are administered according to an intermittent dosing regimen. The term “intermittent dosing regimen” refers to repeating cycles of drug administration in which the drug is administered on one or more consecutive days (“days on”) followed by one or more consecutive days of rest on which the drug is not administered (“days off”). The cycles may be regular, in that the pattern of days on and days off is the same in each cycle, or may be irregular. In embodiments, the cycle is 21 days and the Talabostat or the pharmaceutically acceptable salt thereof is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 consecutive days followed by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 days where the patient takes no Talabostat. In embodiments, this intermittent dosing schedule occurs multiple times within the same cycle. For example, in embodiments, the cycle is 21 days and Pembrolizumab is administered intravenously on day 1 and the Talabostat or the pharmaceutically acceptable salt thereof is administered for 3 consecutive days followed by 4 days where the patient Attorney Reference: ONKO-003/01WO takes no Talabostat, and this 7 day pattern repeats once (i.e. no Talabostat is administered on days 15-21) or twice. In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is administered orally (e.g. by tablet) on each of days 1 to 14 and the Pembrolizumab is administered intravenously on day 1 and no drug is administered on days 15-21. [0158] In embodiments, Pembrolizumab may conveniently be administered as a single dose in the regimen of this disclosure to effectively treat a subject afflicted with pancreatic cancer. In embodiments, the Pembrolizumab is administered intravenously on day 1 where no drug is administered on days 15-21. [0159] In embodiments, the Pembrolizumab may be administered at a total dose of about 1 mg/kg to about 10 mg/kg per day, conveniently by injection (e.g., intravenously), most preferably as continuous infusion for 30 minutes. A suitable dose of the Pembrolizumab administered intravenously in the treatment regimen of the present disclosure may conveniently be from about 100 mg to about 500 mg, e.g. about 200 mg per day. [0160] In embodiments, the total dose of Pembrolizumab administered intravenously in the treatment regimen of the present disclosure may conveniently be from about 100 mg to about 500 mg, about 150 mg to about 500 mg, about 200 mg to about 500 mg, about 250 mg to about 500 mg, about 300 mg to about 500 mg, about 350 mg to about 500 mg, about 400 mg to about 500 mg, about 450 mg to about 500 mg. [0161] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) may be administered at a total daily dose of about 0.001 mg/kg to about 0.1 mg/kg (e.g. about 0.001 mg/kg to about 0.035 mg/kg, or about 0.001 mg/kg to about 0.014 mg/kg), conveniently by the oral route (e.g. tablet). A suitable daily dose of the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) administered orally via one or more (e.g. two or three) tablets in the treatment regimen of the present disclosure may conveniently be from about 0.1 mg to about 1 mg (e.g. about 0.05mg, about 0.1 mg, about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, preferably about 0.1 mg to about 0.6 mg, more preferably about 0.4 mg to about 0.6 mg). In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) may be administered orally at a dose of about 0.2 mg twice daily in divided doses In Attorney Reference: ONKO-003/01WO embodiments, the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) may be administered orally at a dose of about 0.3 mg twice daily in divided doses. In embodiment, the Talabostat or the pharmaceutically acceptable salt thereof may be administered orally at a dose of about 0.2 mg thrice daily in divided doses. In embodiment, the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) may be administered orally twice daily, such as at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening in a day. [0162] Suitable treatment regimens for treating a human patient afflicted with pancreatic cancer include, for example, administering to the patient, an effective amount of each of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab, wherein the regimen comprises at least one administration cycle (e.g. 1, 2, 3, 4, 5, 6 or more cycles), wherein each cycle is a period of about 21 days, and wherein for each cycle, the Talabostat or the pharmaceutically acceptable salt thereof is administered orally (e.g. by tablet) on each of days 1 to 14 and the Pembrolizumab is administered intravenously on day 1. [0163] In embodiments, during one or more treatment cycles of about 21 days, the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) is administered on days 1 to 14 at a total daily dose of about 0.4 mg to about 0.6 mg and the Pembrolizumab is administered on day 1 at a total dose of about 100 mg to about 500 mg per day, e.g. about 200 mg per day. [0164] In embodiments, the daily dose of Talabostat or a pharmaceutically acceptable salt thereof may be varied over time. For example, during the first cycle (including the Lead-in Stage) the Talabostat or the pharmaceutically acceptable salt thereof may be administered at a lower daily dose than during subsequent cycles (e.g. Efficacy Stage). For example, the Talabostat or the pharmaceutically acceptable salt thereof may conveniently be administered during the Lead-in Stage a daily dose of about 0.4 mg, and, if there are no side effects or other criteria preventing further treatment, the subject is allowed to enter the Efficacy Stage and administered, during Efficacy Stage, a daily dose of about 0.6 mg (for e.g. administered in split doses as 0.3 mg twice daily). In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof may be administered during the Lead-in Stage a daily dose of about 0.6 mg and during the Efficacy Stage Attorney Reference: ONKO-003/01WO a daily dose of about 0.4 mg. In embodiments, the patient is treated directly in the Efficacy Stage using a daily dose of about 0.4 mg or about 0.6 mg. [0165] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab are administered to a subject afflicted with pancreatic cancer (e.g., pancreatic ductal carcinoma) in any desired number of treatment cycles as long as a clinical benefit is observed or until there is a complete response, confirmed progressive disease or unmanageable toxicity. [0166] In embodiments, the daily dosages of the Talabostat or the pharmaceutically acceptable salt thereof (Talabostat mesylate) and the Pembrolizumab used according to the treatment regimen of this disclosure may be lower than the daily dosages of one or both of the Talabostat or the pharmaceutically acceptable salt thereof (e.g. Talabostat mesylate) and the Pembrolizumab administered as single agents to treat a subject afflicted with pancreatic cancer (e.g., pancreatic ductal carcinoma) [0167] In embodiments, the combination therapy is preferably administered for at least 12 weeks (three 4-week cycles or four 3-week cycles), more preferably at least 24 weeks (six 4-week cycles or eight 3-week cycles), and even more preferably at least 1 to 4 weeks after the patient achieves a complete response. [0168] In embodiments, a single administration cycle comprises 21 days (21- day cycle). In embodiments, Talabostat mesylate is administered once daily (QD) on Days 1 to 14 of a 21-day cycle plus Pembrolizumab as 200 mg administered intravenously (IV) on Day 1 every 21 days. [0169] In embodiments, a single administration cycle comprises 21 days (21- day cycle). In embodiment, Talabostat mesylate is administered twice daily at a dose of 0.3 mg on Days 1 to 14 of a 21-day cycle plus Pembrolizumab 200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, Talabostat mesylate is administered thrice daily at a dose of about 0.2 mg on Days 1 to 14 of a 21-day cycle plus Pembrolizumab 200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, Talabostat mesylate is administered at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening on Days 1 to 14 of a 21-day cycle plus Pembrolizumab 200 mg administered intravenously (IV) on Day 1 every 21 days. In embodiment, Attorney Reference: ONKO-003/01WO Talabostat mesylate is administered at a dose of about 0.2 mg in the morning and about 0.4 mg in the evening on Days 1 to 14 of a 21-day cycle plus Pembrolizumab 200 mg administered intravenously (IV) on Day 1 every 21 days. [0170] In embodiments, Talabostat mesylate is administered twice daily at a dose of about 0.3 mg on Days 1 to 3 of a 21-day cycle plus Pembrolizumab 200 mg administered intravenously (IV) on Day 1 every 21 days followed by rest period from day 4-7 (no dose of Talabostat given) and then followed by Talabostat mesylate is administered twice daily at a dose of about 0.3 mg on Days 8 to 11 of a 21-day cycle. [0171] In embodiments, the combination therapy of the disclosure is administered to a patient who has not been previously treated with a biotherapeutic or chemotherapeutic agent, i.e., is treatment- naive. In embodiments, the combination therapy is administered to a patient who failed to achieve a sustained response after prior therapy with a biotherapeutic or chemotherapeutic agent, i.e., is treatment- experienced. [0172] In embodiments, the subject is treated with a single daily 0.6 mg dose of Talabostat mesylate and experienced dose-limiting side effects. [0173] In embodiments of any of the methods or the regimen described herein, before the period of time, the subject was treated with Talabostat mesylate as a monotherapy, and, optionally, the prior treatment with the Talabostat mesylate as a monotherapy was unsuccessful. In embodiments of any of the methods or the regimen described herein, before the period of time, the patient was treated with Pembrolizumab, or a biosimilar thereof as a monotherapy, and optionally, the prior treatment with Pembrolizumab, or a biosimilar thereof was unsuccessful. [0174] A suitable period of time can be determined by one skilled in the art (e.g., a physician). As can be appreciated in the art, a suitable period of time can be determined by one skilled in the art based on one or more of: the stage of disease in the patient, the mass and sex of the patient, clinical trial guidelines (e.g., those on the fda.gov website), and information on the approved drug label. For example a suitable period of time can be, e.g., from 1 week to 2 years, 1 week to 22 months, 1 week to 20 months, 1 week to 18 months, 1 week to 16 months, 1 week to 14 months, 1 week to 12 months, 1 week to 10 months, 1 week to 8 months, 1 week to 6 months, 1 week to 4 Attorney Reference: ONKO-003/01WO months 1 week to 2 months, 1 week to 1 month, 2 weeks to 2 years, 2 weeks to 22 months, 2 weeks to 20 months, 2 weeks to 18 months, 2 weeks to 16 months, 2 weeks to 14 months, 2 weeks to 12 months, 2 weeks to 10 months, 2 weeks to 8 months, 2 weeks to 6 months, 2 weeks to 4 months, 2 weeks to 2 months, 2 weeks to 1 month, 1 month to 2 years, 1 month to 22 months, 1 month to 20 months, 1 month to 18 months, 1 month to 16 months, 1 month to 14 months, 1 month to 12 months, 1 month to 10 months, 1 month to 8 months, 1 month to 6 months, 1 month to 4 months, 1 month to 2 months, 2 months to 2 years, 2 months to 22 months, 2 months to 20 months, 2 months to 18 months, 2 months to 16 months, 2 months to 14 months, 2 months to 12 months, 2 months to 10 months, 2 months to 8 months, 2 months to 6 months, 2 months to 4 months, 3 months to 2 years, 3 months to 22 months, 3 months to 20 months, 3 months to 18 months, 3 months to 16 months, 3 months to 14 months, 3 months to 12 months, 3 months to 10 months, 3 months to 8 months, 3 months to 6 months, 4 months to 2 years, 4 months to 22 months, 4 months to 20 months, 4 months to 18 months, 4 months to 16 months, 4 months to 14 months, 4 months to 12 months, 4 months to 10 months, 4 months to 8 months, 4 months to 6 months, 6 months to 2 years, 6 months to 22 months, 6 months to 20 months, 6 months to 18 months, 6 months to 16 months, 6 months to 14 months, 6 months to 12 months, 6 months to 10 months, 6 months to 8 months, 8 months to 2 years, 8 months to 22 months, 8 months to 20 months, 8 months to 18 months, 8 months to 16 months, 8 months to 14 months, 8 months to 12 months, 8 months to 10 months, 10 months to 2 years, 10 months to 22 months, 10 months to 20 months, 10 months to 18 months, 10 months to 16 months, 10 months to 14 months, 10 months to 12 months, 12 months to 2 years, 12 months to 22 months, 12 months to 20 months, 12 months to 18 months, 12 months to 16 months, or 12 months to 14 months, inclusive. 4. Pharmaceutical formulations A. SCLC [0175] In embodiments, the present disclosure provides for use in the treatment regimen herein a pharmaceutical formulation comprising an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist together with one or more pharmaceutically acceptable carriers or adjuvants. In embodiments, the PD-1 axis antagonist includes PD1 antagonist (for example anti-PD-1 antibody), PD-L1 antagonist (for Attorney Reference: ONKO-003/01WO example anti-PD-Ll antibody) and PD-L2 antagonist (for example anti-PD-L2 antibody). Any of the pharmaceutically acceptable carriers or adjuvants described herein, or known in the art, may be used. As used herein, the term "pharmaceutical formulation" refers to a formulation comprising Talabostat or a pharmaceutically acceptable salt thereof or a formulation comprising Atezolizumab, wherein each formulation also comprises one or more pharmaceutically acceptable carriers or adjuvants. Pharmaceutically acceptable carriers or adjuvants are well-known to those skilled in the art, and usually depend on the chosen route of administration. [0176] In embodiments, a first formulation comprising Talabostat or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or adjuvants and a second formulation comprising a PD-L1 antagonist and one or more pharmaceutically acceptable carriers or adjuvants are administered according to the treatment regimen disclosed herein to produce a synergistic effect in treating a subject afflicted with small cell lung cancer (e.g. ES- SCLC). [0177] In embodiments, the PD-L1 antagonist is selected from the group consisting of Avelumab, Durvalumab or Atezolizumab. In embodiments, the PD-L1 antagonist is Atezolizumab. [0178] In embodiments, a first formulation comprising Talabostat or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or adjuvants and a second formulation comprising Atezolizumab and one or more pharmaceutically acceptable carriers or adjuvants are administered according to the treatment regimen disclosed herein to produce a synergistic effect in treating a subject afflicted with small cell lung cancer (e.g. ES- SCLC). [0179] The pharmaceutical formulations may be formulated in a variety of ways, including for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. In embodiments, the compositions may be formulated as the injectable or infusible solutions. The formulation is in a form suitable for oral, intravenous, intraarterial, intramuscular, subcutaneous, parenteral, transmucosal, transdermal, or topical administration. The formulation may be formulated as an immediate, controlled, extended or delayed release composition. Attorney Reference: ONKO-003/01WO [0180] In embodiments, the formulation comprising Talabostat or a pharmaceutically acceptable salt thereof may be administered orally. In embodiments, the formulation comprising Atezolizumab may be administered parenterally. As used herein, the term "parenteral" includes subcutaneous, intravenous, intra-arterial, intraperitoneal, intracardiac, intrathecal, and intramuscular injection, as well as infusion injections. [0181] Liquid pharmaceutical formulations for parenteral administration may be formulated for administration by injection or continuous infusion. In embodiments, parenteral formulations can include prefilled syringes, vials, powder for infusion for reconstitution, concentrate for infusion to be diluted before delivery (ready to dilute), solutions (ready to use). [0182] Injectable pharmaceutical formulations can be aqueous isotonic solutions or suspensions, and suppositories can be prepared from fatty emulsions or suspensions. [0183] Pharmaceutical formulations formulated for parenteral administration (e.g. via intravenous injection) may conveniently include a liquid carrier, or may be reconstituted into a liquid solution or suspension for parenteral administration. [0184] In general, such formulations typically comprise a pharmaceutically acceptable carrier or adjuvant. As used herein, the term “pharmaceutically acceptable" means approved by a government regulatory agency or listed in the U.S. Pharmacopoeia or another generally recognized pharmacopoeia for use in animals, particularly in humans. [0185] Pharmaceutical formulations of Atezolizumab for intravenous administration may be purchased from the marketplace or prepared using conventional formulation techniques. Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, chlorobutanol, thimerosal, alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol and m- cresol; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino Attorney Reference: ONKO-003/01WO acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; chelating agents such as EDTA; monosaccharides, disaccharides, and other carbohydrates including sugars such as sucrose, mannitol, trehalose or sorbitol, glucose, mannose, or dextrins; salt-forming counter-ions such as sodium; metal complexes (for example., Zn-protein complexes); and/or non-ionic surfactants such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable carriers herein further include interstitial drug dispersion agents such as soluble neutral-active hyaluronidase glycoproteins (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoproteins, such as rHuPH20 (HYLENEX®, Baxter International, Inc.). The carrier can be a solvent or reconstitution medium or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. More particularly, the pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In such cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It should be stable under the conditions of manufacture and storage and will preferably be preserved against the contaminating action of microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycol, or the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Suitable formulations for use in the therapeutic methods disclosed herein are described in Remington's Pharmaceutical Sciences, Mack Publishing Co., 16th ed. (1980). [0186] In embodiments, the formulation includes isotonic agents, for example, sugars, polyalcohols, such as mannitol, sorbitol, or sodium chloride. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin. [0187] Sterile injectable solutions can be prepared by incorporating the molecule, by itself or in combination with other active agents, in the required amount in an appropriate solvent with one Attorney Reference: ONKO-003/01WO or a combination of ingredients enumerated herein, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle, which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, one method of preparation is vacuum drying and freeze-drying, which yields a powder of an active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The preparations for injections are processed, filled into containers such as ampoules, bags, bottles, syringes or vials, and sealed under aseptic conditions according to methods known in the art. Such articles of manufacture will preferably have labels or package inserts indicating that the associated compositions are useful for treating a subject suffering from or predisposed to autoimmune or neoplastic disorders. The pharmaceutical formulations may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they may also contain other therapeutically valuable substances. [0188] Solution or suspension formulations used for subcutaneous application typically include one or more of the following components: a sterile carrier such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerin, propylene glycol, or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates; and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. Such preparations may be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. [0189] Pharmaceutical formulations of Talabostat or a pharmaceutically acceptable salt thereof for oral use herein may be administered, for example, in the form of tablets, capsules, powders, dispersible granules, sachets etc., or as aqueous solutions or suspensions, preferably tablets. Oral compositions generally include an inert carrier (for example, diluent) or an edible carrier. The formulations may be enclosed in a gelatin capsule or compressed into a tablet. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the formulation. The tablets, pills, capsules, granules, sachets, troches and the like can contain any Attorney Reference: ONKO-003/01WO of the following ingredients, or compounds of a similar nature; a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, primogel, or corn starch; a lubricant such as magnesium stearate or stearates; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring. [0190] In embodiments, an oral pharmaceutical formulation comprising Talabostat or pharmaceutically acceptable salt thereof described herein may comprise one or more pharmaceutically acceptable carriers or adjuvants selected from the group comprising a bulking agent, buffer, surfactant, and pH modifier. The pharmaceutical formulation may be adjusted to give an appropriate pH. [0191] In embodiments, the Talabostat or the pharmaceutically acceptable salt thereof is formulated as a tablet for oral administration according to the treatment regimen of this disclosure. The pharmaceutical tablet may be an immediate release or a modified release tablet. Tablet may be in the form of matrix or coated form. [0192] In embodiments, the various processes of making above mentioned formulations or compositions are included and such formulations can be manufactured by any of the processes known in the art. [0193] An exemplary immediate release tablet comprises an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers selected from diluents, binders, disintegrants, glidants, lubricants, pH modifying agents and combinations thereof. [0194] Diluents: one or more diluents comprise, but are not limited to dibasic calcium phosphate, pullulan, maltodextrin, isomalt, sugar pellets, mannitol, spray-dried mannitol, microcrystalline cellulose, dibasic calcium phosphate dihydrate, lactose, sugars, sorbitol, mixture of microcrystalline cellulose and guar gum (Avicel CE-15), mixture of mannitol, polyplasdone and syloid (Pharmaburst), mixture of mannitol, crospovidone and polyvinyl acetate (Ludiflash), isomalt, Panexcea, F-Melt, sucrose, calcium salts and similar inorganic salts, heavy magnesium Attorney Reference: ONKO-003/01WO carbonate and the like, and the mixtures thereof. Preferably, it is lactose or microcrystalline cellulose. [0195] Binders: one or more binders comprise, but are not limited to, low-substituted hydroxypropyl cellulose, xanthan gum, polyvinylpyrrolidone (povidone), gelatin, sugars, glucose, natural gums, gums, synthetic celluloses, polymethacrylate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methyl cellulose, and other cellulose derivatives and the like, and the mixtures thereof. Preferably, the binder is polyvinylpyrrolidone or hydroxypropyl cellulose or hydroxypropyl methylcellulose. [0196] Disintegrants: one or more binders comprise, but are not limited to, at least one or a mixture of sodium starch glycolate, croscarmellose sodium, crospovidone, sodium alginate, gums, starch, and magnesium aluminium silicate. Preferably, the disintegrant is sodium starch glycolate. [0197] Lubricants: one or lubricants comprise, but are not limited to sodium stearyl fumarate, sodium lauryl sulphate, magnesium stearate, polyethylene glycol, metal stearates, hydrogenated castor oil and the like, and the mixtures thereof. Preferably, the lubricant is magnesium stearate. [0198] Glidant: one or glidants comprise, but are not limited to, stearic acid, colloidal silicon dioxide, talc, aluminium silicate and the like, and the mixtures thereof. Preferably, it is talc. [0199] pH modifying agents: one or more pH modifying agents comprise, but are not limited to organic acid or its salts like phosphoric acid, citric acid and the like. [0200] In embodiments, the relative percentages of the ingredients in tablet formulations of Talabostat is given below in Table 1: Table 1:

Attorney Reference: ONKO-003/01WO

An exemplary immediate release tablet of Talabostat mesylate is given below in Table 2: Table 2:

[0201] In embodiments, Talabostat or a pharmaceutically acceptable salt thereof may be formulated as a modified release matrix tablet. An exemplary extended release tablet comprises an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and pharmaceutically-acceptable carrier or adjuvant are selected from the diluents, binders, modified release material, glidants, lubricants, colorants and combinations thereof. Alternatively, a modified release tablet comprises immediate release core and coating wherein said coating comprises modified release material and other pharmaceutical excipients. [0202] Modified release materials comprise, but are not limited to: polyvinylpyrrolidone (K90), hydroxypropylmethylcellulose (K4M, K10), hydroxypropylcellulose (high viscosity grade), carnauba wax, glyceryl behenate, castor wax, polyvinyl acetate, carboxymethyl ethyl cellulose, ethylcellulose, cellulose phthalates or succinates, in particular cellulose acetate phthalate and hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose succinate or hydroxypropylmethylcellulose acetate succinate; high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and copolymers of ethylene oxide and propylene Attorney Reference: ONKO-003/01WO oxide and the like. Particular modified release materials include polyvinylpyrrolidone (K90), hydroxypropylmethylcellulose (K4M, K10), hydroxypropylcellulose (high viscosity grade-HF), polyethylene oxide and the like. A modified release material may conveniently be present in the range of 10-50% wt. of the tablet. [0203] An exemplary modified release tablet of Talabostat or a pharmaceutically acceptable salt thereof is given below in Table 3: Table 3:

[0204] In embodiments, the amount of Talabostat in a unit dose is about 50 micrograms, about 100 micrograms per tablet, about 200 micrograms per tablet, about 300 micrograms per tablet, about 400 micrograms per tablet, about 500 micrograms per tablet, about 600 micrograms per tablet, about 700 micrograms per tablet, about 800 micrograms per tablet. [0205] Various methods can be used for manufacturing tablets of the Talabostat or the pharmaceutically acceptable salt thereof for use in the treatment regimen of this disclosure. One process includes dissolving Talabostat in a suitable solvent (with or without binder) and this solution is distributed uniformly over filler particles (which may contain other materials) to form agglomerated particles/granules. Wet granulation, coating or spraying processes can also be used. Granules may be appropriately sized or may be further processed by a dry Attorney Reference: ONKO-003/01WO granulation/slugging/roller compaction method followed by a milling step to achieve suitable granules of specific particle size distribution. The sized granules may be further blended with other components and/or and then lubricated in a suitable blender and compressed into tablets of specific dimensions using appropriate tooling. Coating of the tablets, where appropriate, may be performed using conventional methods and standard equipment. B) Pancreatic cancer [0206] In embodiments, the present disclosure provides for use in the treatment regimen herein a pharmaceutical formulation comprising an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist together with one or more pharmaceutically acceptable carriers or adjuvants. In embodiments, the PD-1 axis antagonist includes PD-1 antagonist (for example anti-PD-1 antibody), PD-Ll antagonist (for example anti-PD-L1 antibody) and PD-L2 antagonist (for example anti-PD-L2 antibody). Any of the pharmaceutically acceptable carriers or adjuvants described herein, or known in the art, may be used. As used herein, the term "pharmaceutical formulation" refers to a formulation comprising Talabostat or a pharmaceutically acceptable salt thereof or a formulation comprising Pembrolizumab, wherein each formulation also comprises one or more pharmaceutically acceptable carriers or adjuvants. Pharmaceutically acceptable carriers or adjuvants are well-known to those skilled in the art, and usually depend on the chosen route of administration. [0207] In embodiments, a first formulation comprising Talabostat or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or adjuvants and a second formulation comprising Pembrolizumab, and one or more pharmaceutically acceptable carriers or adjuvants are administered according to the treatment regimen disclosed herein to produce a synergistic effect in treating a subject afflicted with pancreatic cancer (e.g., pancreatic ductal carcinoma). [0208] The pharmaceutical formulations may be formulated in a variety of ways, including for example, liquid, semi-solid and solid dosage forms, such as liquid solutions (e.g., injectable and infusible solutions), dispersions or suspensions, tablets, pills, powders, liposomes and suppositories. In embodiments, the compositions may be formulated as the injectable or infusible solutions. The formulation is in a form suitable for oral, intravenous, intraarterial, intramuscular, Attorney Reference: ONKO-003/01WO subcutaneous, parenteral, transmucosal, transdermal, or topical administration. The formulation may be formulated as an immediate, controlled, extended or delayed release composition. [0209] In embodiments, the formulation comprising Talabostat or a pharmaceutically acceptable salt thereof may be administered orally. In embodiments, the formulation comprising Pembrolizumab may be administered parenterally. As used herein, the term "parenteral" includes subcutaneous, intravenous, intra-arterial, intraperitoneal, intracardiac, intrathecal, and intramuscular injection, as well as infusion injections. [0210] Liquid pharmaceutical formulations for parenteral administration may be formulated for administration by injection or continuous infusion. In embodiments, parenteral formulations can include prefilled syringes, vials, powder for infusion for reconstitution, concentrate for infusion to be diluted before delivery (ready to dilute), solutions (ready to use). [0211] Injectable pharmaceutical formulations can be aqueous isotonic solutions or suspensions, and suppositories can be prepared from fatty emulsions or suspensions. [0212] Pharmaceutical formulations formulated for parenteral administration (e.g. via intravenous injection) may conveniently include a liquid carrier, or may be reconstituted into a liquid solution or suspension for parenteral administration. [0213] In general, such formulations typically comprise a pharmaceutically acceptable carrier or adjuvant. As used herein, the term “pharmaceutically acceptable" means approved by a government regulatory agency or listed in the U.S. Pharmacopoeia or another generally recognized pharmacopoeia for use in animals, particularly in humans. [0214] Pharmaceutical formulations of Pembrolizumab for intravenous administration may be purchased from the marketplace or prepared using conventional formulation techniques. Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl or benzyl alcohol, chlorobutanol, thimerosal, alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol and m- Attorney Reference: ONKO-003/01WO cresol; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; chelating agents such as EDTA; monosaccharides, disaccharides, and other carbohydrates including sugars such as sucrose, mannitol, trehalose or sorbitol, glucose, mannose, or dextrins; salt-forming counter-ions such as sodium; metal complexes (for example., Zn-protein complexes); and/or non-ionic surfactants such as polyethylene glycol (PEG). Exemplary pharmaceutically acceptable carriers herein further include interstitial drug dispersion agents such as soluble neutral-active hyaluronidase glycoproteins (sHASEGP), for example, human soluble PH-20 hyaluronidase glycoproteins, such as rHuPH20 (HYLENEX®, Baxter International, Inc.). The carrier can be a solvent or reconstitution medium or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. More particularly, the pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In such cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It should be stable under the conditions of manufacture and storage and will preferably be preserved against the contaminating action of microorganisms, such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycol, or the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Suitable formulations for use in the therapeutic methods disclosed herein are described in Remington's Pharmaceutical Sciences, Mack Publishing Co., 16th ed. (1980). [0215] In embodiments, the formulation includes isotonic agents, for example, sugars, polyalcohols, such as mannitol, sorbitol, or sodium chloride. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminium monostearate and gelatin. Attorney Reference: ONKO-003/01WO [0216] Sterile injectable solutions can be prepared by incorporating the molecule, by itself or in combination with other active agents, in the required amount in an appropriate solvent with one or a combination of ingredients enumerated herein, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle, which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, one method of preparation is vacuum drying and freeze-drying, which yields a powder of an active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof. The preparations for injections are processed, filled into containers such as ampoules, bags, bottles, syringes or vials, and sealed under aseptic conditions according to methods known in the art. Such articles of manufacture will preferably have labels or package inserts indicating that the associated compositions are useful for treating a subject suffering from or predisposed to autoimmune or neoplastic disorders. The pharmaceutical formulations may be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they may also contain other therapeutically valuable substances. [0217] Solution or suspension formulations used for subcutaneous application typically include one or more of the following components: a sterile carrier such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerin, propylene glycol, or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates; and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. Such preparations may be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. 5. Kits [0218] In embodiments, the kit includes a formulation comprising Talabostat or pharmaceutically acceptable salt thereof and a formulation comprising PD-1 axis antagonist (for example anti-PD-1 antibody), PD-Ll antagonist (for example anti-PD-Ll antibody) and PD-L2 Attorney Reference: ONKO-003/01WO antagonist (for example anti-PD-L2 antibody) with or without instructions for their use. In embodiments, the kit includes a formulation comprising Talabostat or pharmaceutically acceptable salt thereof and a formulation comprising PD-Ll antagonist (for example Atezolizumab) with or without instructions for their use. In embodiments, the kit includes a formulation comprising Talabostat or pharmaceutically acceptable salt thereof and a formulation comprising PD-l antagonist (for example Pembrolizumab) with or without instructions for their use. The combined therapeutics can be manufactured and/or formulated by the same or different manufacturers. The combination therapeutics may thus be entirely separate pharmaceutical dosage forms or pharmaceutical compositions that are also sold independently of each other. In embodiments, instructions for their combined use are provided: (i) prior to release to physicians (e.g. in the case of a "kit of part" comprising a first therapeutic agent and the other therapeutic agent); (ii) by the physicians themselves (or under the guidance of a physician) shortly before administration; (iii) the patient themselves by a physician or medical staff. [0219] In one example, a single bolus dose may be administered. In another example, several divided doses may be administered over time. In yet another example, a dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. Dosage unit form, as used herein, refers to physically discrete units suited as unitary dosages for treating mammalian subjects. Each unit may contain a predetermined quantity of active compound calculated to produce a desired therapeutic effect. In embodiments, the dosage unit forms of the disclosure are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic or prophylactic effect to be achieved. [0220] In embodiments, the kit comprises a package insert comprising instructions for using the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. In embodiments, the kit comprises the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab and package insert comprising instructions for using the same to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. In embodiments, the kit comprises the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab, and a package insert comprising instructions for using the same to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. Attorney Reference: ONKO-003/01WO [0221] In embodiments, the kit comprises a package insert comprising instructions for using the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. In embodiments, the kit comprises the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab and package insert comprising instructions for using the same to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. In embodiments, the kit comprises the Talabostat or pharmaceutically acceptable salt thereof and the Pembrolizumab, and a package insert comprising instructions for using the same to treat or delay progression of cancer in a subject or to enhance immune function of a subject having cancer. [0222] In embodiments, the kit comprises a container that includes, but is not limited to bottles, vials (e.g., dual chamber vials), syringes (such as single or dual chamber syringes) and test tubes. The container may be formed from a variety of materials such as glass or plastic. In embodiments, the kit may comprise a label (e.g., on or associated with the container) or a package insert. The label or the package insert may indicate that the compound contained therein may be useful or intended for treating or delaying progression of cancer in a subject or for enhancing immune function of a subject having cancer. The kit may further comprise other materials desirable from a commercial and user standpoint, including other buffers, diluents, filters, needles, and syringes. 6. Outcomes A) SCLC [0223] Patients afflicted with small cell lung cancer (SCLC) administered Talabostat or a pharmaceutically acceptable salt thereof and PD-L1 antagonist (for example Atezolizumab) according to the treatment regimen disclosed herein preferably experience improvement in at least one sign of cancer. [0224] Patients afflicted with small cell lung cancer (SCLC) administered Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab according to the treatment regimen disclosed herein preferably experience improvement in at least one sign of cancer. In embodiment, improvement may be measured by a reduction in the quantity and/or size of measurable tumor Attorney Reference: ONKO-003/01WO lesions. In embodiment, lesions can be measured using x-rays or CT or MRI scans. In embodiment, cytology or histology can be used to evaluate responsiveness to the therapy. In embodiment, extension of progression free survival and/or overall survival may be provided to a patient afflicted with small cell lung cancer. In embodiment, extension of progression free survival and/or overall survival may be provided to a patient afflicted with small cell lung cancer. [0225] In embodiments, the anti-tumor response is a tumor specific response, a clinical response, a decrease in tumor size/volume, a decrease in tumor specific biomarkers, increase in anti-tumor cytokines or a combination thereof. [0226] In embodiments, the clinical response is a decreased tumor growth and/or a decrease in tumor size. In embodiments, the initiating, sustaining or enhancing an anti-tumor immune response is for the treatment of small cell lung cancer. [0227] In embodiments, the anti-tumor response is inhibiting tumor growth, inducing tumor cell death, tumor regression, preventing or delaying tumor recurrence, tumor growth, tumor spread or tumor elimination. [0228] In embodiments, the anti-tumor response is reduction in metastasis, delay in metastasis or prevention of metastasis. In embodiments, the anti-tumor response is prevention of metastasis. [0229] In embodiments, the tumor response is a decrease in the number of tumor cells. In embodiments, the tumor response is a decreased rate in tumor growth. In embodiments, the tumor response is a block in the dipeptidyl peptidase enzyme activity. In embodiments, the tumor response is an induction of proinflammatory cytokine response and a cytotoxic T cell response. [0230] The treatment regimen described herein may result in an inhibition of tumor size more than about 10%, more than about 20%, more than about 21%, more than about 22%, more than about 23% , more than about 24%, more than about 25%, more than about 26%, more than about 27%, more than about 28%, more than about 29%, more than about 30%, more than about 31%, more than about 32%, more than about 33% , more than about 34%, more than about 35%, more than about 36%, more than about 37%, more than about 38%, more than about 39%, more than about 40%, more than about 41%, more than about 42%, more than about 43%, more than about 44%, more than about 45%, more than about 46%, more than about 47%, more than about 48%, Attorney Reference: ONKO-003/01WO more than about 49%, more than about 50%, more than about 51%, more than about 52%, more than about 53%, more than about 54%, more than about 55%, more than about 56%, more than about 57%, more than about 58%, more than about 59%, more than about 60%, more than about 61%, more than about 62%, more than about 63%, more than about 64%, more than about 65%, more than 66%, more than 67%, more than 68%, more than 69%, more than about 70%, more than about 71%, more than about 72%, more than about 73%, more than about 74%, more than about 75%, more than about 76%, more than about 77%, more than about 78%, more than about 79%, more than about 80%, more than about 81%, more than about 82%, more than about 83%, more than about 84%, more than about 85%, more than more than about 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than about 95%, more than 96%, more than 97%, more than 98%, more than 99% up to about 100%. [0231] In embodiments, the regimen and the methods provided herein can result in a 1 % to 99% (e.g., 1 % to 98%, 1 % to 95%, 1 % to 90%, 1 to 85%, 1 to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to 30%, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 2% to 99%, 2% to 90%, 2% to 85%, 2% to 80%, 2% to 75%, 2% to 70%, 2% to 65%, 2% to 60%, 2% to 55%, 2% to 50%, 2% to 45%, 2% to 40%, 2% to 35%, 2% to 30%, 2% to 25%, 2% to 20%, 2% to 15%, 2% to 10%, 2% to 5%, 4% to 99%, 4% to 95%, 4% to 90%, 4% to 85%, 4% to 80%, 4% to 75%, 4% to 70%, 4% to 65%, 4% to 60%, 4% to 55%, 4% to 50%, 4% to 45%, 4% to 40%, 4% to 35%, 4% to 30%, 4% to 25%, 4% to 20%, 4% to 15%, 4% to 10%, 6% to 99%, 6% to 95%, 6% to 90%, 6% to 85%, 6% to 80%, 6% to 75%, 6% to 70%, 6% to 65%, 6% to 60%, 6% to 55%, 6% to 50%, 6% to 45%, 6% to 40%, 6% to 35%, 6% to 30%, 6% to 25%, 6% to 20%, 6% to 15%, 6% to 10%, 8% to 99%, 8% to 95%, 8% to 90%, 8% to 85%, 8% to 80%, 8% to 75%, 8% to 70%, 8% to 65%, 8% to 60%, 8% to 55%, 8% to 50%, 8% to 45%, 8% to 40%, 8% to 35%, 8% to 30%, 8% to 25%, 8% to 20%, 8% to 15%, 10% to 99%, 10% to 95%, 10% to 90%, 10% to 85%, 10% to 80%, 10% to 75%, 10% to 70%, 10% to 65%, 10% to 60%, 10% to 55%, 10% to 50%, 10% to 45%, 10% to 40%, 10% to 35%, 10% to 30%, 10% to 25%, 10% to 20%, 10% to 15%, 15% to 99%, 15% to 95%, 15% to 90%, 15% to 85%, 15% to 80%, 15% to 75%, 15% to 70%, 15% to 65%, 15% to 60%, 15% to 55%, 15% to 50%, 15% to 55%, 15% to 50%, 15% to 45%, 15% to 40%, 15% to 35%, 15% to 30%, 15% to 25%, 15% to 20%, 20% to 99%, 20% to 95%, 20% to 90%, 20% to 85%, 20% to 80%, 20% to 75%, 20% to 70%, 20% to 65%, 20% to 60%, 20% to 55%, 20% to 50%, 20% to Attorney Reference: ONKO-003/01WO 45%, 20% to 40%, 20% to 35%, 20% to 30%, 20% to 25%, 25% to 99%, 25% to 95%, 25% to 90%, 25% to 85%, 25% to 80%, 25% to 75%, 25% to 70%, 25% to 65%, 25% to 60%, 25% to 55%, 25% to 50%, 25% to 45%, 25% to 40%, 25% to 35%, 25% to 30%, 30% to 99%, 30% to 95%, 30% to 90%, 30% to 85%, 30% to 80%, 30% to 75%, 30% to 70%, 30% to 65%, 30% to 60%, 30% to 55%, 30% to 50%, 30% to 45%, 30% to 40%, 30% to 35%, 35% to 99%, 35% to 95%, 35% to 90%, 35% to 85%, 35% to 80%, 35% to 75%, 35% to 70%, 35% to 65%, 35% to 60%, 35% to 55%, 35% to 50%, 35% to 45%, 35% to 40%, 40% to 99%, 40% to 95%, 40% to 90%, 40% to 85%, 40% to 80%, 40% to 75%, 40% to 70%, 40% to 65%, 40% to 60%, 40% to 55%, 40% to 60%, 40% to 55%, 40% to 50%, 40% to 45%, 45% to 99%, 45% to 95%, 45% to 95%, 45% to 90%, 45% to 85%, 45% to 80%, 45% to 75%, 45% to 70%, 45% to 65%, 45% to 60%, 45% to 55%, 45% to 50%, 50% to 99%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to 80%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 50% to 55%, 55% to 99%, 55% to 95%, 55% to 90%, 55% to 85%, 55% to 80%, 55% to 75%, 55% to 70%, 55% to 65%, 55% to 60%, 60% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 65% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 70% to 99%, 70% to 95%, 70% to 90%, 70% to 85%, 70% to 80%, 70% to 75%, 75% to 99%, 75% to 95%, 75% to 90%, 75% to 85%, 75% to 80%, 80% to 99%, 80% to 95%, 80% to 90%, 80% to 85%, 85% to 99%, 85% to 95%, 85% to 90%, 90% to 99%, 90% to 95%, or 95% to 100%) reduction in the volume of small cell lung cancer (SCLC) in a patient following treatment with the combination therapy for a period of time between 1 day and 2 years (e.g., between 1 day and 22 months, between 1 day and 20 months, between 1 day and 18 months, between 1 day and 16 months, between 1 day and 14 months, between 1 day and 12 months, between 1 day and 10 months, between 1 day and 9 months, between 1 day and 8 months, between 1 day and 7 months, between 1 day and 6 months, between 1 day and 5 months, between 1 day and 4 months, between 1 day and 3 months, between 1 day and 2 months, between 1 day and 1 month, between one week and 2 years, between 1 week and 22 months, between 1 week and 20 months, between 1 week and 18 months, between 1 week and 16 months, between 1 week and 14 months, between 1 week and 12 months, between 1 week and 10 months, between 1 week and 9 months, between 1 week and 8 months, between 1 week and 7 months, between 1 week and 6 months, between 1 week and 5 months, between 1 week and 4 months, between 1 week and 3 months, between 1 week and 2 months, between 1 week and 1 month, between 2 weeks and 2 Attorney Reference: ONKO-003/01WO years, between 2 weeks and 22 months, between 2 weeks and 20 months, between 2 weeks and 18 months, between 2 weeks and 16 months, between 2 weeks and 14 months, between 2 weeks and 12 months, between 2 weeks and 10 months, between 2 weeks and 9 months, between 2 weeks and 8 months, between 2 weeks and 7 months, between 2 weeks and 6 months, between 2 weeks and 5 months, between 2 weeks and 4 months, between 2 weeks and 3 months, between 2 weeks and 2 months, between 2 weeks and 1 month, between 1 month and 2 years, between 1 month and 22 months, between 1 month and 20 months, between 1 month and 18 months, between 1 month and 16 months, between 1 month and 14 months, between 1 month and 12 months, between 1 month and 10 months, between 1 month and 9 months, between 1 month and 8 months, between 1 month and 7 months, between 1 month and 6 months, between 1 month and 6 months, between 1 month and 5 months, between 1 month and 4 months, between 1 month and 3 months, between 1 month and 2 months, between 2 months and 2 years, between 2 months and 22 months, between 2 months and 20 months, between 2 months and 18 months, between 2 months and 16 months, between 2 months and 14 months, between 2 months and 12 months, between 2 months and 10 months, between 2 months and 9 months, between 2 months and 8 months, between 2 months and 7 months, between 2 months and 6 months, or between 2 months and 5 months, between 2 months and 4 months, between 3 months and 2 years, between 3 months and 22 months, between 3 months and 20 months, between 3 months and 18 months, between 3 months and 16 months, between 3 months and 14 months, between 3 months and 12 months, between 3 months and 10 months, between 3 months and 8 months, between 3 months and 6 months, between 4 months and 2 years, between 4 months and 22 months, between 4 months and 20 months, between 4 months and 18 months, between 4 months and 16 months, between 4 months and 14 months, between 4 months and 12 months, between 4 months and 10 months, between 4 months and 8 months, between 4 months and 6 months, between 6 months and 2 years, between 6 months and 22 months, between 6 months and 20 months, between 6 months and 18 months, between 6 months and 16 months, between 6 months and 14 months, between 6 months and 12 months, between 6 months and 10 months, or between 6 months and 8 months) (e.g., as compared to the size of the SCLC in the patient prior to treatment). [0232] In embodiments, the regimen or the methods provided herein can provide for a 1 % to 99% (e.g. , 1 % to 98%, 1 % to 95%, 1 % to 90%, 1 to 85%, 1 to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to Attorney Reference: ONKO-003/01WO %, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 2% to 99%, 2% to 90%, 2% 85%, 2% to 80%, 2% to 75%, 2% to 70%, 2% to 65%, 2% to 60%, 2% to 55%, 2% to 50%, 2% 45%, 2% to 40%, 2% to 35%, 2% to 30%, 2% to 25%, 2% to 20%, 2% to 15%, 2% to 10%, 2% 5%, 4% to 99%, 4% to 95%, 4% to 90%, 4% to 85%, 4% to 80%, 4% to 75%, 4% to 70%, 4% 65%, 4% to 60%, 4% to 55%, 4% to 50%, 4% to 45%, 4% to 40%, 4% to 35%, 4% to 30%, 4% 25%, 4% to 20%, 4% to 15%, 4% to 10%, 6% to 99%, 6% to 95%, 6% to 90%, 6% to 85%, 6% 80%, 6% to 75%, 6% to 70%, 6% to 65%, 6% to 60%, 6% to 55%, 6% to 50%, 6% to 45%, 6% 40%, 6% to 35%, 6% to 30%, 6% to 25%, 6% to 20%, 6% to 15%, 6% to 10%, 8% to 99%, 8% 95%, 8% to 90%, 8% to 85%, 8% to 80%, 8% to 75%, 8% to 70%, 8% to 65%, 8% to 60%, 8% 55%, 8% to 50%, 8% to 45%, 8% to 40%, 8% to 35%, 8% to 30%, 8% to 25%, 8% to 20%, 8% 15%, 10% to 99%, 10% to 95%, 10% to 90%, 10% to 85%, 10% to 80%, 10% to 75%, 10% to%, 10% to 65%, 10% to 60%, 10% to 55%, 10% to 50%, 10% to 45%, 10% to 40%, 10% to%, 10% to 30%, 10% to 25%, 10% to 20%, 10% to 15%, 15% to 99%, 15% to 95%, 15% to%, 15% to 85%, 15% to 80%, 15% to 75%, 15% to 70%, 15% to 65%, 15% to 60%, 15% to%, 15% to 50%, 15% to 55%, 15% to 50%, 15% to 45%, 15% to 40%, 15% to 35%, 15% to%, 15% to 25%, 15% to 20%, 20% to 99%, 20% to 95%, 20% to 90%, 20% to 85%, 20% to%, 20% to 75%, 20% to 70%, 20% to 65%, 20% to 60%, 20% to 55%, 20% to 50%, 20% to%, 20% to 40%, 20% to 35%, 20% to 30%, 20% to 25%, 25% to 99%, 25% to 95%, 25% to%, 25% to 85%, 25% to 80%, 25% to 75%, 25% to 70%, 25% to 65%, 25% to 60%, 25% to%, 25% to 50%, 25% to 45%, 25% to 40%, 25% to 35%, 25% to 30%, 30% to 99%, 30% to%, 30% to 90%, 30% to 85%, 30% to 80%, 30% to 75%, 30% to 70%, 30% to 65%, 30% to%, 30% to 55%, 30% to 50%, 30% to 45%, 30% to 40%, 30% to 35%, 35% to 99%, 35% to%, 35% to 90%, 35% to 85%, 35% to 80%, 35% to 75%, 35% to 70%, 35% to 65%, 35% to%, 35% to 55%, 35% to 50%, 35% to 45%, 35% to 40%, 40% to 99%, 40% to 95%, 40% to%, 40% to 85%, 40% to 80%, 40% to 75%, 40% to 70%, 40% to 65%, 40% to 60%, 40% to%, 40% to 60%, 40% to 55%, 40% to 50%, 40% to 45%, 45% to 99%, 45% to 95%, 45% to%, 45% to 90%, 45% to 85%, 45% to 80%, 45% to 75%, 45% to 70%, 45% to 65%, 45% to%, 45% to 55%, 45% to 50%, 50% to 99%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 50% to 55%, 55% to 99%, 55% to%, 55% to 90%, 55% to 85%, 55% to 80%, 55% to 75%, 55% to 70%, 55% to 65%, 55% to%, 60% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to Attorney Reference: ONKO-003/01WO 70%, 60% to 65%, 65% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 70% to 99%, 70% to 95%, 70% to 90%, 70% to 85%, 70% to 80%, 70% to 75%, 75% to 99%, 75% to 95%, 75% to 90%, 75% to 85%, 75% to 80%, 80% to 99%, 80% to 95%, 80% to 90%, 80% to 85%, 85% to 99%, 85% to 95%, 85% to 90%, 90% to 99%, 90% to 95%, or 95% to 100%) reduction in the risk of developing a metastasis or the risk of developing an additional metastasis in a patient having small cell lung cancer (SCLC) . [0233] In embodiments, the treatment regimen or the methods described herein can result in an increase (e.g. , a 1 % to 400%, 1 % to 380%, 1 % to 360%, 1 % to 340%, 1 % to 320%, 1 % to 300%, 1 % to 280%, 1 % to 260%, 1 % to 240%, 1 % to 220%, 1 % to 200%, 1 % to 180%, 1 % to 160%, 1 % to 140%, 1 % to 120%, 1 % to 100%, 1 % to 95%, 1 % to 90%, 1 % to 85%, 1 % to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to 30%, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 5% to 400%, 5% to 380%, 5% to 360%, 5% to 340%, 5% to 320%, 5% to 300%, 5% to 280%, 5% to 260%, 5% to 240%, 5% to 220%, 5% to 200%, 5% to 180%, 5% to 160%, 5% to 140%, 5% to 120%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 10%, 10% to 400%, 10% to 380%, 10% to 360%, 10% to 340%, 10% to 320%, 10% to 300%, 10% to 280%, 10% to 260%, 10% to 240%, 10% to 220%, 10% to 200%, 10% to 180%, 10% to 160%, 10% to 140%, 10% to 120%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 20% to 400%, 20% to 380%, 20% to 360%, 20% to 340%, 20% to 320%, 20% to 300%, 20% to 280%, 20% to 260%, 20% to 240%, 20% to 220%, 20% to 200%, 20% to 180%, 20% to 160%, 20% to 140%, 20% to 120%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 400%, 30% to 380%, 30% to 360%, 30% to 340%, 30% to 320%, 30% to 300%, 30% to 280%, 30% to 260%, 30% to 240%, 30% to 220%, 30% to 200%, 30% to 180%, 30% to 160%, 30% to 140%, 30% to 120%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 400%, 40% to 380%, 40% to 360%, 40% to 340%, 40% to 320%, 40% to 300%, 40% to 280%, 40% to 260%, 40% to 240%, 40% to 220%, 40% to 200%, 40% to 180%, 40% to 160%, 40% to 140%, 40% to 120%, 40% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 400%, 50% to 380%, 50% to 360%, 50% to 340%, 50% to 320%, 50% to 300%, 50% to 280%, 50% to 260%, 50% to 240%, 50% to 220%, 50% to 200%, 50% to 180%, 50% to 160%, 50% to 140%, Attorney Reference: ONKO-003/01WO % to 140%, 50% to 120%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%,% to 400%, 60% to 380%, 60% to 360%, 60% to 340%, 60% to 320%, 60% to 300%, 60% to0%, 60% to 260%, 60% to 240%, 60% to 220%, 60% to 200%, 60% to 180%, 60% to 160%,% to 140%, 60% to 120%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 400%,% to 380%, 70% to 360%, 70% to 340%, 70% to 320%, 70% to 300%, 70% to 280%, 70% to0%, 70% to 240%, 70% to 220%, 70% to 200%, 70% to 180%, 70% to 160%, 70% to 140%,% to 120%, to 100%, 70% to 90%, 70% to 80%, 80% to 400%, 80% to 380%, 80% to 360%,% to 340%, 80% to 320%, 80% to 300%, 80% to 280%, 80% to 260%, 80% to 240%, 80% to0%, 80% to 200%, 80% to 180%, 80% to 160%, 80% to 140%, 80% to 120%, 80% to 100%,% to 90%, 90% to 400%, 90% to 380%, 90% to 360%, 90% to 340%, 90% to 320%, 90% to0%, 90% to 280%, 90% to 260%, 90% to 240%, 90% to 220%, 90% to 200%, 90% to 180%,% to 160%, 90% to 140%, 90% to 120%, 90% to 100%, 100% to 400%, 100% to 380%, 100% 360%, 100% to 340%, 100% to 320%, 100% to 300%, 100% to 280%, 100% to 260%, 100% 240%, 100% to 220%, 100% to 200%, 100% to 180%, 100% to 160%, 100% to 140%, 100% 120%, 120% to 400%, 120% to 380%, 120% to 360%, 120% to 340%, 120% to 320%, 120% 300%, 120% to 280%, 120% to 260%, 120% to 240%, 120% to 220%, 120% to 200%, 120% 180%, 120% to 160%, 120% to 140%, 140% to 400%, 140% to 380%, 140% to 360%, 140% 340%, 140% to 320%, 140% to 300%, 140% to 280%, 140% to 260%, 140% to 240%, 140% 220%, 140% to 200%, 140% to 180%, 140% to 160%, 160% to 400%, 160% to 380%, 160% 360%, 160% to 340%, 160% to 320%, 160% to 300%, 160% to 280%, 160% to 260%, 160% 240%, 160% to 220%, 160% to 200%, 160% to 180%, 180% to 400%, 180% to 380%, 180% 360%, 180% to 340%, 180% to 320%, 180% to 300%, 180% to 280%, 180% to 260%, 180% 240%, 180% to 220%, 180% to 200%, 200% to 400%, 200% to 380%, 200% to 360%, 200% 340%, 200% to 320%, 200% to 300%, 200% to 280%, 200% to 260%, 200% to 240%, 200% 220%, 220% to 400%, 220% to 380%, 220% to 360%, 220% to 340%, 220% to 320%, 220% 300%, 220% to 280%, 220% to 260%, 220% to 240%, 240% to 400%, 240% to 380%, 240% 360%, 240% to 340%, 240% to 320%, 240% to 300%, 240% to 280%, 240% to 260%, 260% 400%, 260% to 380%, 260% to 360%, 260% to 340%, 260% to 320%, 260% to 300%, 260% 280%, 280% to 400%, 280% to 380%, 280% to 360%, 280% to 340%, 280% to 320%, 280% 300%, 300% to 400%, 300% to 380%, 300% to 360%, 300% to 340%, or 300% to 320%) in the Attorney Reference: ONKO-003/01WO time of survival of the patient (e.g., as compared to a patient having a similar cancer and administered a different treatment or not receiving a treatment). [0234] In embodiment, patients afflicted with small cell lung cancer (SCLC) administered 0.3 mg twice daily dose of Talabostat or a pharmaceutically acceptable salt thereof on one or more days of a treatment cycle, and an effective amount of Atezolizumab according to the treatment regimen disclosed herein may exhibit a complete response (CR), a partial response (PR), stable disease (SD), immune-related complete disease (irCR), immune-related partial response (irPR), or immune-related stable disease (irSD). [0235] In embodiments, patients afflicted with small cell lung cancer (SCLC) administered Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab according to the treatment regimen disclosed herein may experience tumor shrinkage and/or decrease in growth rate, i.e., suppression of tumor growth. In embodiment, unwanted cell proliferation may be reduced or inhibited. [0236] In embodiments, one or more of the following may occur in patients afflicted with small cell lung cancer (SCLC) administered Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab according to the treatment regimen disclosed herein: the number of cancer cells may be reduced; tumor size may be reduced; cancer cell infiltration into peripheral organs may be inhibited, retarded, slowed, or stopped; tumor metastasis may be slowed or inhibited; tumor growth may be inhibited; recurrence of tumor may be prevented or delayed; one or more of the symptoms associated with cancer may be alleviated. [0237] In embodiments, the patients afflicted with small cell lung cancer (SCLC) administered the Talabostat orthe pharmaceutically acceptable salt thereof and the Atezolizumab according to the treatment regimen disclosed herein may exhibit at least one therapeutic effect selected from the group consisting of reduction in size of a tumor, reduction in number of metastatic lesions appearing over time, complete remission, partial remission, or stable disease. [0238] In embodiments, the treatment regimen herein may produce a comparable clinical EHQHILW^ UDWH^ ^&%5 &5^35^6'^ ^^^ PRQWKV^^ EHWWHU^ WKDQ^ WKDW^ DFKLHYHG^ E\^ 7DODERVWDW^ RU^ D^ pharmaceutically acceptable salt thereof, or Atezolizumab alone. Attorney Reference: ONKO-003/01WO [0239] In embodiments, the improvement of clinical benefit rate achieved using the treatment regimen of the present disclosure may be about 20%, 30%, 40%, 50%, 60%, 70%, 80% or more compared to treatment using Talabostat or Atezolizumab alone. [0240] In embodiments, the treatment regimen of the present disclosure may result in the CD8+ T cells in the subject having enhanced priming, activation, proliferation and/or cytolytic activity when compared to administration of the Talabostat or the pharmaceutically acceptable salt thereof, or the Atezolizumab alone. [0241] In embodiments, the number of CD4+ and/or CD8+ T cells is elevated relative to prior to administration of the combination. [0242] In embodiments, the activated CD4+ and/or CD8+ T cells is characterized by y-IFN+ producing CD4+ and/or CD8+ T cells and/or enhanced cytolytic activity relative to prior to the administration of the combination. [0243] In embodiments, the CD4+ and/or CD8+ T cells exhibit increased release of cytokines selected from the group consisting of G-CSF, MCP-1, Eotaxin, IFN-Ȗ^^ .&^ TNF-Į^ DQG^ interleukins (IL-5, IL-6, IL-^ȕ^^,/-12p70, IL 18). [0244] In embodiments, the CD4+ and/or CD8+ T cell is an effector memory T cell. In HPERGLPHQWV^^ WKH^ &'^^^ DQG^RU^ &'^^^ HIIHFWRU^ PHPRU\^ 7^ FHOO^ LV^ FKDUDFWHUL]HG^ E\^ Ȗ- IFN+ producing CD4+ and/or CD8+ T cells and/or enhanced cytolytic activity. [0245] In embodiments, the serum levels of cytokine IL-18 and/or chemokine GM-CSF, G- CSF in the subject are increased in the presence of combination of the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab as compared to single agent administration. [0246] In embodiments, the cancer has elevated levels of T-cell infiltration when a combination of the Talabostat or the pharmaceutically acceptable salt thereof, and the Atezolizumab is used according to the treatment regimen described herein, when compared to administration of the Talabostat or the Atezolizumab alone. Attorney Reference: ONKO-003/01WO [0247] In embodiments, the cancer has suppressed/decreased levels of T-regulatory cells in the presence of the combination of Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab when used according to the treatment regimen described herein, when compared to administration of the Talabostat or the pharmaceutically acceptable salt thereof, or the Atezolizumab alone. In embodiments, the cancer has increased levels of NK cells and macrophages in the presence of combination of the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab when used according to the treatment regimen described herein, when compared to administration of the Talabostat orthe pharmaceutically acceptable salt thereof, or the Atezolizumab alone. [0248] Tumor response evaluation is performed using the following RECIST definitions. [0249] The duration of overall response was measured from the time measurement criteria was first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). [0250] The duration of overall CR is measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. [0251] In embodiment, the patients afflicted with small cell lung cancer (SCLC) administered according to the treatment regimen achieves a stable disease response or better, as measured by RECIST 1.1. [0252] In embodiments, the patients afflicted with small cell lung cancer (SCLC) administered according to the treatment regimen achieves a partial disease response or better, as measured by RECIST 1.1. [0253] In embodiments, the patients afflicted with small cell lung cancer (SCLC) administered according to the treatment regimen achieves a complete response or better, as measured by RECIST 1.1. [0254] Stable disease was measured from the start of the treatment until the criteria for progression were met, taking as reference the smallest sum on study (if the baseline sum was the smallest, this was the reference for calculation of PD). Attorney Reference: ONKO-003/01WO [0255] With respect to target lesions, responses to the treatment regimen described herein may include: Complete response (CR), Partial Response (PR), Progressive Disease (PD), Stable Disease (SD), Immune-related Complete Response (irCR), Immune-related Partial Response (irPR), Immune-related Progressive Disease (irPD) and Immune-related Stable Disease (irSD). [0256] With respect to non-target lesions, responses to the treatment regimen described herein may include: Complete Response (CR), Progressive Disease (PD), Immune-related Complete Response (irCR) and Immune-related Progressive Disease (irPD). [0257] In embodiment, the patient treated exhibits a complete response (CR), a partial response (PR), stable disease (SD), immune-related complete disease (irCR), immune-related partial response (irPR), or immune-related stable disease (irSD). In embodiment, the patient treated experiences tumor shrinkage and/or decrease in growth rate, i.e., suppression of tumor growth. In embodiment, unwanted cell proliferation is reduced or inhibited. In embodiment, one or more of the following can occur: the number of cancer cells can be reduced; tumor size can be reduced; cancer cell infiltration into peripheral organs can be inhibited, retarded, slowed, or stopped; tumor metastasis can be slowed or inhibited; tumor growth can be inhibited; recurrence of tumor can be prevented or delayed; one or more of the symptoms associated with cancer can be relieved to some extent. [0258] In embodiments, the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg daily dose of Talabostat. Pro-inflammatory cytokines contemplated within the scope of this invention are readily apparent to a person of ordinary skill in the art, and include, but are not limited to IL-6, IL-8, IL-18, IFN-Ȗ^^DQG^,/-^ȕ^^^,Q^ embodiments, the pro-inflammatory cytokines are one or more of IL-18 and IFN- Ȗ^^ ^ ,n embodiments, the maximum increase in cytokines is observed at day 14 of continuous dosing. B) Pancreatic cancer [0259] Patients afflicted with pancreatic cancer administered Talabostat or a pharmaceutically acceptable salt thereof and PD-1 antagonist ) according to the treatment regimen disclosed herein preferably experience improvement in at least one sign of cancer. Attorney Reference: ONKO-003/01WO [0260] Patients afflicted with the pancreatic cancer administered the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab according to the treatment regimen disclosed herein preferably experience improvement in at least one sign of cancer. In embodiment, improvement may be measured by a reduction in the quantity and/or size of measurable tumor lesions. In embodiment, lesions can be measured using x-rays or CT or MRI scans. In embodiment, cytology or histology can be used to evaluate responsiveness to the therapy. In embodiment, extension of progression free survival and/or overall survival may be provided to a patient afflicted with pancreatic cancer. In embodiment, extension of progression free survival and/or overall survival may be provided to a patient afflicted with pancreatic cancer. [0261] In embodiments, the anti-tumor response is a tumor specific response, a clinical response, a decrease in tumor size/volume, a decrease in tumor specific biomarkers, increase in anti-tumor cytokines or a combination thereof. [0262] In embodiments, the clinical response is a decreased tumor growth and/or a decrease in tumor size. In embodiments, the initiating, sustaining or enhancing an anti-tumor immune response is for the treatment of the pancreatic cancer. [0263] In embodiments, the anti-tumor response is inhibiting tumor growth, inducing tumor cell death, tumor regression, preventing or delaying tumor recurrence, tumor growth, tumor spread or tumor elimination. [0264] In embodiments, the anti-tumor response is reduction in metastasis, delay in metastasis or prevention of metastasis. In embodiments, the anti-tumor response is prevention of metastasis. [0265] In embodiments, the tumor response is a decrease in the number of tumor cells. In embodiments, the tumor response is a decreased rate in tumor growth. In embodiments, the tumor response is a block in the dipeptidyl peptidase enzyme activity. In embodiments, the tumor response is an induction of proinflammatory cytokine response and a cytotoxic T cell response. [0266] The treatment regimen described herein may result in an inhibition of tumor size more than about 10%, more than about 20%, more than about 21%, more than about 22%, more than about 23% , more than about 24%, more than about 25%, more than about 26%, more than about 27%, more than about 28%, more than about 29%, more than about 30%, more than about 31%, Attorney Reference: ONKO-003/01WO more than about 32%, more than about 33% , more than about 34%, more than about 35%, more than about 36%, more than about 37%, more than about 38%, more than about 39%, more than about 40%, more than about 41%, more than about 42%, more than about 43%, more than about 44%, more than about 45%, more than about 46%, more than about 47%, more than about 48%, more than about 49%, more than about 50%, more than about 51%, more than about 52%, more than about 53%, more than about 54%, more than about 55%, more than about 56%, more than about 57%, more than about 58%, more than about 59%, more than about 60%, more than about 61%, more than about 62%, more than about 63%, more than about 64%, more than about 65%, more than 66%, more than 67%, more than 68%, more than 69%, more than about 70%, more than about 71%, more than about 72%, more than about 73%, more than about 74%, more than about 75%, more than about 76%, more than about 77%, more than about 78%, more than about 79%, more than about 80%, more than about 81%, more than about 82%, more than about 83%, more than about 84%, more than about 85%, more than more than about 90%, more than 91%, more than 92%, more than 93%, more than 94%, more than about 95%, more than 96%, more than 97%, more than 98%, more than 99% up to about 100%. [0267] In embodiments, the regimen and the methods provided herein can result in a 1 % to 99% (e.g., 1 % to 98%, 1 % to 95%, 1 % to 90%, 1 to 85%, 1 to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to 30%, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 2% to 99%, 2% to 90%, 2% to 85%, 2% to 80%, 2% to 75%, 2% to 70%, 2% to 65%, 2% to 60%, 2% to 55%, 2% to 50%, 2% to 45%, 2% to 40%, 2% to 35%, 2% to 30%, 2% to 25%, 2% to 20%, 2% to 15%, 2% to 10%, 2% to 5%, 4% to 99%, 4% to 95%, 4% to 90%, 4% to 85%, 4% to 80%, 4% to 75%, 4% to 70%, 4% to 65%, 4% to 60%, 4% to 55%, 4% to 50%, 4% to 45%, 4% to 40%, 4% to 35%, 4% to 30%, 4% to 25%, 4% to 20%, 4% to 15%, 4% to 10%, 6% to 99%, 6% to 95%, 6% to 90%, 6% to 85%, 6% to 80%, 6% to 75%, 6% to 70%, 6% to 65%, 6% to 60%, 6% to 55%, 6% to 50%, 6% to 45%, 6% to 40%, 6% to 35%, 6% to 30%, 6% to 25%, 6% to 20%, 6% to 15%, 6% to 10%, 8% to 99%, 8% to 95%, 8% to 90%, 8% to 85%, 8% to 80%, 8% to 75%, 8% to 70%, 8% to 65%, 8% to 60%, 8% to 55%, 8% to 50%, 8% to 45%, 8% to 40%, 8% to 35%, 8% to 30%, 8% to 25%, 8% to 20%, 8% to 15%, 10% to 99%, 10% to 95%, 10% to 90%, 10% to 85%, 10% to 80%, 10% to 75%, 10% to 70%, 10% to 65%, 10% to 60%, 10% to 55%, 10% to 50%, 10% to 45%, 10% to 40%, 10% to 35%, 10% to 30%, 10% to 25%, 10% to 20%, 10% to 15%, 15% to 99%, 15% to 95%, 15% to Attorney Reference: ONKO-003/01WO 90%, 15% to 85%, 15% to 80%, 15% to 75%, 15% to 70%, 15% to 65%, 15% to 60%, 15% to 55%, 15% to 50%, 15% to 55%, 15% to 50%, 15% to 45%, 15% to 40%, 15% to 35%, 15% to 30%, 15% to 25%, 15% to 20%, 20% to 99%, 20% to 95%, 20% to 90%, 20% to 85%, 20% to 80%, 20% to 75%, 20% to 70%, 20% to 65%, 20% to 60%, 20% to 55%, 20% to 50%, 20% to 45%, 20% to 40%, 20% to 35%, 20% to 30%, 20% to 25%, 25% to 99%, 25% to 95%, 25% to 90%, 25% to 85%, 25% to 80%, 25% to 75%, 25% to 70%, 25% to 65%, 25% to 60%, 25% to 55%, 25% to 50%, 25% to 45%, 25% to 40%, 25% to 35%, 25% to 30%, 30% to 99%, 30% to 95%, 30% to 90%, 30% to 85%, 30% to 80%, 30% to 75%, 30% to 70%, 30% to 65%, 30% to 60%, 30% to 55%, 30% to 50%, 30% to 45%, 30% to 40%, 30% to 35%, 35% to 99%, 35% to 95%, 35% to 90%, 35% to 85%, 35% to 80%, 35% to 75%, 35% to 70%, 35% to 65%, 35% to 60%, 35% to 55%, 35% to 50%, 35% to 45%, 35% to 40%, 40% to 99%, 40% to 95%, 40% to 90%, 40% to 85%, 40% to 80%, 40% to 75%, 40% to 70%, 40% to 65%, 40% to 60%, 40% to 55%, 40% to 60%, 40% to 55%, 40% to 50%, 40% to 45%, 45% to 99%, 45% to 95%, 45% to 95%, 45% to 90%, 45% to 85%, 45% to 80%, 45% to 75%, 45% to 70%, 45% to 65%, 45% to 60%, 45% to 55%, 45% to 50%, 50% to 99%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to 80%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 50% to 55%, 55% to 99%, 55% to 95%, 55% to 90%, 55% to 85%, 55% to 80%, 55% to 75%, 55% to 70%, 55% to 65%, 55% to 60%, 60% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 65% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 70% to 99%, 70% to 95%, 70% to 90%, 70% to 85%, 70% to 80%, 70% to 75%, 75% to 99%, 75% to 95%, 75% to 90%, 75% to 85%, 75% to 80%, 80% to 99%, 80% to 95%, 80% to 90%, 80% to 85%, 85% to 99%, 85% to 95%, 85% to 90%, 90% to 99%, 90% to 95%, or 95% to 100%) reduction in the volume of pancreatic cancer in a patient following treatment with the combination therapy for a period of time between 1 day and 2 years (e.g., between 1 day and 22 months, between 1 day and 20 months, between 1 day and 18 months, between 1 day and 16 months, between 1 day and 14 months, between 1 day and 12 months, between 1 day and 10 months, between 1 day and 9 months, between 1 day and 8 months, between 1 day and 7 months, between 1 day and 6 months, between 1 day and 5 months, between 1 day and 4 months, between 1 day and 3 months, between 1 day and 2 months, between 1 day and 1 month, between one week and 2 years, between 1 week and 22 months, between 1 week and 20 months, between 1 week and 18 months, between 1 week and 16 months, between 1 week and 14 Attorney Reference: ONKO-003/01WO months, between 1 week and 12 months, between 1 week and 10 months, between 1 week and 9 months, between 1 week and 8 months, between 1 week and 7 months, between 1 week and 6 months, between 1 week and 5 months, between 1 week and 4 months, between 1 week and 3 months, between 1 week and 2 months, between 1 week and 1 month, between 2 weeks and 2 years, between 2 weeks and 22 months, between 2 weeks and 20 months, between 2 weeks and 18 months, between 2 weeks and 16 months, between 2 weeks and 14 months, between 2 weeks and 12 months, between 2 weeks and 10 months, between 2 weeks and 9 months, between 2 weeks and 8 months, between 2 weeks and 7 months, between 2 weeks and 6 months, between 2 weeks and 5 months, between 2 weeks and 4 months, between 2 weeks and 3 months, between 2 weeks and 2 months, between 2 weeks and 1 month, between 1 month and 2 years, between 1 month and 22 months, between 1 month and 20 months, between 1 month and 18 months, between 1 month and 16 months, between 1 month and 14 months, between 1 month and 12 months, between 1 month and 10 months, between 1 month and 9 months, between 1 month and 8 months, between 1 month and 7 months, between 1 month and 6 months, between 1 month and 6 months, between 1 month and 5 months, between 1 month and 4 months, between 1 month and 3 months, between 1 month and 2 months, between 2 months and 2 years, between 2 months and 22 months, between 2 months and 20 months, between 2 months and 18 months, between 2 months and 16 months, between 2 months and 14 months, between 2 months and 12 months, between 2 months and 10 months, between 2 months and 9 months, between 2 months and 8 months, between 2 months and 7 months, between 2 months and 6 months, or between 2 months and 5 months, between 2 months and 4 months, between 3 months and 2 years, between 3 months and 22 months, between 3 months and 20 months, between 3 months and 18 months, between 3 months and 16 months, between 3 months and 14 months, between 3 months and 12 months, between 3 months and 10 months, between 3 months and 8 months, between 3 months and 6 months, between 4 months and 2 years, between 4 months and 22 months, between 4 months and 20 months, between 4 months and 18 months, between 4 months and 16 months, between 4 months and 14 months, between 4 months and 12 months, between 4 months and 10 months, between 4 months and 8 months, between 4 months and 6 months, between 6 months and 2 years, between 6 months and 22 months, between 6 months and 20 months, between 6 months and 18 months, between 6 months and 16 months, between 6 months and 14 months, between 6 months and 12 months, between 6 months and 10 Attorney Reference: ONKO-003/01WO months, or between 6 months and 8 months) (e.g., as compared to the size of the pancreatic cancer in the patient prior to treatment). [0268] In embodiments, the regimen or the methods provided herein can provide for a 1 % to 99% (e.g. , 1 % to 98%, 1 % to 95%, 1 % to 90%, 1 to 85%, 1 to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to 30%, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 2% to 99%, 2% to 90%, 2% to 85%, 2% to 80%, 2% to 75%, 2% to 70%, 2% to 65%, 2% to 60%, 2% to 55%, 2% to 50%, 2% to 45%, 2% to 40%, 2% to 35%, 2% to 30%, 2% to 25%, 2% to 20%, 2% to 15%, 2% to 10%, 2% to 5%, 4% to 99%, 4% to 95%, 4% to 90%, 4% to 85%, 4% to 80%, 4% to 75%, 4% to 70%, 4% to 65%, 4% to 60%, 4% to 55%, 4% to 50%, 4% to 45%, 4% to 40%, 4% to 35%, 4% to 30%, 4% to 25%, 4% to 20%, 4% to 15%, 4% to 10%, 6% to 99%, 6% to 95%, 6% to 90%, 6% to 85%, 6% to 80%, 6% to 75%, 6% to 70%, 6% to 65%, 6% to 60%, 6% to 55%, 6% to 50%, 6% to 45%, 6% to 40%, 6% to 35%, 6% to 30%, 6% to 25%, 6% to 20%, 6% to 15%, 6% to 10%, 8% to 99%, 8% to 95%, 8% to 90%, 8% to 85%, 8% to 80%, 8% to 75%, 8% to 70%, 8% to 65%, 8% to 60%, 8% to 55%, 8% to 50%, 8% to 45%, 8% to 40%, 8% to 35%, 8% to 30%, 8% to 25%, 8% to 20%, 8% to 15%, 10% to 99%, 10% to 95%, 10% to 90%, 10% to 85%, 10% to 80%, 10% to 75%, 10% to 70%, 10% to 65%, 10% to 60%, 10% to 55%, 10% to 50%, 10% to 45%, 10% to 40%, 10% to 35%, 10% to 30%, 10% to 25%, 10% to 20%, 10% to 15%, 15% to 99%, 15% to 95%, 15% to 90%, 15% to 85%, 15% to 80%, 15% to 75%, 15% to 70%, 15% to 65%, 15% to 60%, 15% to 55%, 15% to 50%, 15% to 55%, 15% to 50%, 15% to 45%, 15% to 40%, 15% to 35%, 15% to 30%, 15% to 25%, 15% to 20%, 20% to 99%, 20% to 95%, 20% to 90%, 20% to 85%, 20% to 80%, 20% to 75%, 20% to 70%, 20% to 65%, 20% to 60%, 20% to 55%, 20% to 50%, 20% to 45%, 20% to 40%, 20% to 35%, 20% to 30%, 20% to 25%, 25% to 99%, 25% to 95%, 25% to 90%, 25% to 85%, 25% to 80%, 25% to 75%, 25% to 70%, 25% to 65%, 25% to 60%, 25% to 55%, 25% to 50%, 25% to 45%, 25% to 40%, 25% to 35%, 25% to 30%, 30% to 99%, 30% to 95%, 30% to 90%, 30% to 85%, 30% to 80%, 30% to 75%, 30% to 70%, 30% to 65%, 30% to 60%, 30% to 55%, 30% to 50%, 30% to 45%, 30% to 40%, 30% to 35%, 35% to 99%, 35% to 95%, 35% to 90%, 35% to 85%, 35% to 80%, 35% to 75%, 35% to 70%, 35% to 65%, 35% to 60%, 35% to 55%, 35% to 50%, 35% to 45%, 35% to 40%, 40% to 99%, 40% to 95%, 40% to 90%, 40% to 85%, 40% to 80%, 40% to 75%, 40% to 70%, 40% to 65%, 40% to 60%, 40% to 55%, 40% to 60%, 40% to 55%, 40% to 50%, 40% to 45%, 45% to 99%, 45% to 95%, 45% to Attorney Reference: ONKO-003/01WO 95%, 45% to 90%, 45% to 85%, 45% to 80%, 45% to 75%, 45% to 70%, 45% to 65%, 45% to 60%, 45% to 55%, 45% to 50%, 50% to 99%, 50% to 95%, 50% to 90%, 50% to 85%, 50% to 80%, 50% to 75%, 50% to 70%, 50% to 65%, 50% to 60%, 50% to 55%, 55% to 99%, 55% to 95%, 55% to 90%, 55% to 85%, 55% to 80%, 55% to 75%, 55% to 70%, 55% to 65%, 55% to 60%, 60% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 65% to 99%, 60% to 95%, 60% to 90%, 60% to 85%, 60% to 80%, 60% to 75%, 60% to 70%, 60% to 65%, 70% to 99%, 70% to 95%, 70% to 90%, 70% to 85%, 70% to 80%, 70% to 75%, 75% to 99%, 75% to 95%, 75% to 90%, 75% to 85%, 75% to 80%, 80% to 99%, 80% to 95%, 80% to 90%, 80% to 85%, 85% to 99%, 85% to 95%, 85% to 90%, 90% to 99%, 90% to 95%, or 95% to 100%) reduction in the risk of developing a metastasis or the risk of developing an additional metastasis in a patient having pancreatic cancer. [0269] In embodiments, the treatment regimen or the methods described herein can result in an increase (e.g. , a 1 % to 400%, 1 % to 380%, 1 % to 360%, 1 % to 340%, 1 % to 320%, 1 % to 300%, 1 % to 280%, 1 % to 260%, 1 % to 240%, 1 % to 220%, 1 % to 200%, 1 % to 180%, 1 % to 160%, 1 % to 140%, 1 % to 120%, 1 % to 100%, 1 % to 95%, 1 % to 90%, 1 % to 85%, 1 % to 80%, 1 % to 75%, 1 % to 70%, 1 % to 65%, 1 % to 60%, 1 % to 55%, 1 % to 50%, 1 % to 45%, 1 % to 40%, 1 % to 35%, 1 % to 30%, 1 % to 25%, 1 % to 20%, 1 % to 15%, 1 % to 10%, 1 % to 5%, 5% to 400%, 5% to 380%, 5% to 360%, 5% to 340%, 5% to 320%, 5% to 300%, 5% to 280%, 5% to 260%, 5% to 240%, 5% to 220%, 5% to 200%, 5% to 180%, 5% to 160%, 5% to 140%, 5% to 120%, 5% to 100%, 5% to 90%, 5% to 80%, 5% to 70%, 5% to 60%, 5% to 50%, 5% to 40%, 5% to 30%, 5% to 20%, 5% to 10%, 10% to 400%, 10% to 380%, 10% to 360%, 10% to 340%, 10% to 320%, 10% to 300%, 10% to 280%, 10% to 260%, 10% to 240%, 10% to 220%, 10% to 200%, 10% to 180%, 10% to 160%, 10% to 140%, 10% to 120%, 10% to 100%, 10% to 90%, 10% to 80%, 10% to 70%, 10% to 60%, 10% to 50%, 10% to 40%, 10% to 30%, 10% to 20%, 20% to 400%, 20% to 380%, 20% to 360%, 20% to 340%, 20% to 320%, 20% to 300%, 20% to 280%, 20% to 260%, 20% to 240%, 20% to 220%, 20% to 200%, 20% to 180%, 20% to 160%, 20% to 140%, 20% to 120%, 20% to 100%, 20% to 90%, 20% to 80%, 20% to 70%, 20% to 60%, 20% to 50%, 20% to 40%, 20% to 30%, 30% to 400%, 30% to 380%, 30% to 360%, 30% to 340%, 30% to 320%, 30% to 300%, 30% to 280%, 30% to 260%, 30% to 240%, 30% to 220%, 30% to 200%, 30% to 180%, 30% to 160%, 30% to 140%, 30% to 120%, 30% to 100%, 30% to 90%, 30% to 80%, 30% to 70%, 30% to 60%, 30% to 50%, 30% to 40%, 40% to 400%, 40% to 380%, Attorney Reference: ONKO-003/01WO % to 360%, 40% to 340%, 40% to 320%, 40% to 300%, 40% to 280%, 40% to 260%, 40% to0%, 40% to 220%, 40% to 200%, 40% to 180%, 40% to 160%, 40% to 140%, 40% to 120%,% to 100%, 40% to 90%, 40% to 80%, 40% to 70%, 40% to 60%, 40% to 50%, 50% to 400%,% to 380%, 50% to 360%, 50% to 340%, 50% to 320%, 50% to 300%, 50% to 280%, 50% to0%, 50% to 240%, 50% to 220%, 50% to 200%, 50% to 180%, 50% to 160%, 50% to 140%,% to 140%, 50% to 120%, 50% to 100%, 50% to 90%, 50% to 80%, 50% to 70%, 50% to 60%,% to 400%, 60% to 380%, 60% to 360%, 60% to 340%, 60% to 320%, 60% to 300%, 60% to0%, 60% to 260%, 60% to 240%, 60% to 220%, 60% to 200%, 60% to 180%, 60% to 160%,% to 140%, 60% to 120%, 60% to 100%, 60% to 90%, 60% to 80%, 60% to 70%, 70% to 400%,% to 380%, 70% to 360%, 70% to 340%, 70% to 320%, 70% to 300%, 70% to 280%, 70% to0%, 70% to 240%, 70% to 220%, 70% to 200%, 70% to 180%, 70% to 160%, 70% to 140%,% to 120%, to 100%, 70% to 90%, 70% to 80%, 80% to 400%, 80% to 380%, 80% to 360%,% to 340%, 80% to 320%, 80% to 300%, 80% to 280%, 80% to 260%, 80% to 240%, 80% to0%, 80% to 200%, 80% to 180%, 80% to 160%, 80% to 140%, 80% to 120%, 80% to 100%,% to 90%, 90% to 400%, 90% to 380%, 90% to 360%, 90% to 340%, 90% to 320%, 90% to0%, 90% to 280%, 90% to 260%, 90% to 240%, 90% to 220%, 90% to 200%, 90% to 180%,% to 160%, 90% to 140%, 90% to 120%, 90% to 100%, 100% to 400%, 100% to 380%, 100% 360%, 100% to 340%, 100% to 320%, 100% to 300%, 100% to 280%, 100% to 260%, 100% 240%, 100% to 220%, 100% to 200%, 100% to 180%, 100% to 160%, 100% to 140%, 100% 120%, 120% to 400%, 120% to 380%, 120% to 360%, 120% to 340%, 120% to 320%, 120% 300%, 120% to 280%, 120% to 260%, 120% to 240%, 120% to 220%, 120% to 200%, 120% 180%, 120% to 160%, 120% to 140%, 140% to 400%, 140% to 380%, 140% to 360%, 140% 340%, 140% to 320%, 140% to 300%, 140% to 280%, 140% to 260%, 140% to 240%, 140% 220%, 140% to 200%, 140% to 180%, 140% to 160%, 160% to 400%, 160% to 380%, 160% 360%, 160% to 340%, 160% to 320%, 160% to 300%, 160% to 280%, 160% to 260%, 160% 240%, 160% to 220%, 160% to 200%, 160% to 180%, 180% to 400%, 180% to 380%, 180% 360%, 180% to 340%, 180% to 320%, 180% to 300%, 180% to 280%, 180% to 260%, 180% 240%, 180% to 220%, 180% to 200%, 200% to 400%, 200% to 380%, 200% to 360%, 200% 340%, 200% to 320%, 200% to 300%, 200% to 280%, 200% to 260%, 200% to 240%, 200% 220%, 220% to 400%, 220% to 380%, 220% to 360%, 220% to 340%, 220% to 320%, 220% 300%, 220% to 280%, 220% to 260%, 220% to 240%, 240% to 400%, 240% to 380%, 240% Attorney Reference: ONKO-003/01WO to 360%, 240% to 340%, 240% to 320%, 240% to 300%, 240% to 280%, 240% to 260%, 260% to 400%, 260% to 380%, 260% to 360%, 260% to 340%, 260% to 320%, 260% to 300%, 260% to 280%, 280% to 400%, 280% to 380%, 280% to 360%, 280% to 340%, 280% to 320%, 280% to 300%, 300% to 400%, 300% to 380%, 300% to 360%, 300% to 340%, or 300% to 320%) in the time of survival of the patient (e.g., as compared to a patient having a similar cancer and administered a different treatment or not receiving a treatment). [0270] In embodiment, the patients afflicted with pancreatic cancer administered 0.3 mg twice daily dose of the Talabostat or the pharmaceutically acceptable salt thereof on one or more days of a treatment cycle, and an effective amount of the Pembrolizumab according to the treatment regimen disclosed herein may exhibit a complete response (CR), a partial response (PR), stable disease (SD), immune-related complete disease (irCR), immune-related partial response (irPR), or immune-related stable disease (irSD). [0271] In embodiments, the patients afflicted with pancreatic cancer administered the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab according to the treatment regimen disclosed herein may experience tumor shrinkage and/or decrease in growth rate, i.e., suppression of tumor growth. In embodiment, unwanted cell proliferation may be reduced or inhibited. [0272] In embodiments, one or more of the following may occur in patients afflicted with pancreatic cancer administered the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab according to the treatment regimen disclosed herein: the number of cancer cells may be reduced; tumor size may be reduced; cancer cell infiltration into peripheral organs may be inhibited, retarded, slowed, or stopped; tumor metastasis may be slowed or inhibited; tumor growth may be inhibited; recurrence of tumor may be prevented or delayed; one or more of the symptoms associated with cancer may be alleviated. [0273] In embodiments, the patients afflicted with pancreatic cancer administered the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab according to the treatment regimen disclosed herein may exhibit at least one therapeutic effect selected from the group consisting of reduction in size of a tumor, reduction in number of metastatic lesions appearing over time, complete remission, partial remission, or stable disease. Attorney Reference: ONKO-003/01WO [0274] In embodiments, the treatment regimen herein may produce a comparable clinical EHQHILW^ UDWH^ ^&%5 &5^35^6'^ ^^^ PRQWKV^^ EHWWHU^ WKDQ^ WKDW^ DFKLHYHG^ E\^ the Talabostat or a pharmaceutically acceptable salt thereof, or the Pembrolizumab alone. [0275] In embodiments, the improvement of clinical benefit rate achieved using the treatment regimen of the present disclosure may be about 20%, 30%, 40%, 50%, 60%, 70%, 80% or more compared to treatment using Talabostat or Pembrolizumab alone. [0276] In embodiments, the treatment regimen of the present disclosure may result in the CD8+ T cells in the subject having enhanced priming, activation, proliferation and/or cytolytic activity when compared to administration of Talabostat or a pharmaceutically acceptable salt thereof, or Pembrolizumab alone. [0277] In embodiments, the number of CD4+ and/or CD8+ T cells is elevated relative to prior to administration of the combination. [0278] In embodiments, the activated CD4+ and/or CD8+ T cells is characterized by y-IFN+ producing CD4+ and/or CD8+ T cells and/or enhanced cytolytic activity relative to prior to the administration of the combination. [0279] In embodiments, the CD4+ and/or CD8+ T cells exhibit increased release of cytokines selected from the group consisting of G-CSF, MCP-1, Eotaxin, IFN-Ȗ^^ .&^^ 71)-Į^ DQG^ interleukins (IL-5, IL-6, IL-^ȕ^^,/-12p70, IL 18). [0280] In embodiments, the CD4+ and/or CD8+ T cell is an effector memory T cell. In some HPERGLPHQWV^^ WKH^ &'^^^ DQG^RU^ &'^^^ HIIHFWRU^ PHPRU\^ 7^ FHOO^ LV^ FKDUDFWHUL]HG^ E\^ Ȗ- IFN+ producing CD4+ and/or CD8+ T cells and/or enhanced cytolytic activity. [0281] In embodiments, the serum levels of cytokine IL-18 and/or chemokine GM-CSF, G- CSF in the subject are increased in the presence of combination of the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab as compared to single agent administration. [0282] In embodiments, the cancer has elevated levels of T-cell infiltration when the combination of the Talabostat or the pharmaceutically acceptable salt thereof, and the Attorney Reference: ONKO-003/01WO Pembrolizumab is used according to the treatment regimen described herein, when compared to administration of Talabostat or Pembrolizumab alone. [0283] In embodiments, the cancer has suppressed/decreased levels of T-regulatory cells in the presence of the combination of theTalabostat orthe pharmaceutically acceptable salt thereof and the Pembrolizumab when used according to the treatment regimen described herein, when compared to administration of Talabostat or the pharmaceutically acceptable salt thereof, or the Pembrolizumab alone. In embodiments, the cancer has increased levels of NK cells and macrophages in the presence of the combination of Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab when used according to the treatment regimen described herein, when compared to administration of the Talabostat or the pharmaceutically acceptable salt thereof, or the Pembrolizumab alone. [0284] Tumor response evaluation is performed using the following RECIST definitions. [0285] The duration of overall response was measured from the time measurement criteria was first met for CR/PR (whichever was first recorded) until the first date that recurrent or PD was objectively documented (taking as reference for PD the smallest measurements recorded on study). [0286] The duration of overall CR is measured from the time measurement criteria were first met for CR until the first date that recurrent disease was objectively documented. [0287] In embodiment, the patients afflicted with pancreatic cancer administered according to the treatment regimen achieves a stable disease response or better, as measured by RECIST 1.1. [0288] In embodiments, the patients afflicted with pancreatic cancer administered according to the treatment regimen achieves a partial disease response or better, as measured by RECIST 1.1. [0289] In embodiments, the patients afflicted with pancreatic cancer administered according to the treatment regimen achieves a complete response or better, as measured by RECIST 1.1. [0290] Stable disease was measured from the start of the treatment until the criteria for progression were met, taking as reference the smallest sum on study (if the baseline sum was the smallest, this was the reference for calculation of PD). Attorney Reference: ONKO-003/01WO [0291] With respect to target lesions, responses to the treatment regimen described herein may include: Complete response (CR), Partial Response (PR), Progressive Disease (PD), Stable Disease (SD), Immune-related Complete Response (irCR), Immune-related Partial Response (irPR), Immune-related Progressive Disease (irPD) and Immune-related Stable Disease (irSD). [0292] With respect to non-target lesions, responses to the treatment regimen described herein may include: Complete Response (CR), Progressive Disease (PD), Immune-related Complete Response (irCR) and Immune-related Progressive Disease (irPD). [0293] In embodiment, the patient treated exhibits a complete response (CR), a partial response (PR), stable disease (SD), immune-related complete disease (irCR), immune-related partial response (irPR), or immune-related stable disease (irSD). In embodiment, the patient treated experiences tumor shrinkage and/or decrease in growth rate, i.e., suppression of tumor growth. In embodiment, unwanted cell proliferation is reduced or inhibited. In embodiment, one or more of the following can occur: the number of cancer cells can be reduced; tumor size can be reduced; cancer cell infiltration into peripheral organs can be inhibited, retarded, slowed, or stopped; tumor metastasis can be slowed or inhibited; tumor growth can be inhibited; recurrence of tumor can be prevented or delayed; one or more of the symptoms associated with cancer can be relieved to some extent. [0294] In embodiments, the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg daily dose of Talabostat. Pro-inflammatory cytokines contemplated within the scope of this invention are readily apparent to a person of ordinary skill in the art, and include, but are not limited to IL-6, IL-8, IL-18, IFN-Ȗ^^DQG^,/-^ȕ^^^,Q^ embodiments, the pro-inflammatory cytokines are one or more of IL-18 and IFN- Ȗ^^ ^ ,Q^ embodiments, wherein the maximum increase in cytokines is observed at day 14 of continuous dosing. SPECIFIC EMBODIMENTS [0295] Embodiment 1: A treatment regimen for treating small cell lung cancer (SCLC) in a subject, the treatment regimen comprising administering to the subject, , an effective amount of Attorney Reference: ONKO-003/01WO Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0296] Embodiment 2: A method of treating small cell lung cancer in a subject,the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0297] Embodiment 3: A method of enhancing an immune response in a subject suffering from small cell lung cancer, the method comprising administering to the subject a regimen comprising an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0298] Embodiment 4: A method of enhancing an innate immune response in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, , an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist, wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells [0299] Embodiment 5: A method of enhancing an innate immune response in a subject with small cell lung cancer (SCLC), the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD- 1 axis antagonist, wherein the enhanced innate immune response is associated with suppression of T-regulatory cells. [0300] Embodiment 6: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with small cell lung cancer (e.g. ES-SCLC), the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0301] Embodiment 7: A method of enhancing immune function in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. Attorney Reference: ONKO-003/01WO [0302] Embodiment 8: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0303] Embodiment 9: A method for reducing the toxicity of Talabostat with a lower effective dose of Talabostat, the method comprising administering to a subject afflicted with small cell lung cancer (SCLC), , effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0304] Embodiment 10: The treatment regimen or the method of treatment according to any of Embodiments 1-9, wherein the PD-1 axis antagonist includes PD1 antagonist, PD-Ll antagonist and PD-L2 antagonist. [0305] Embodiment 11: The treatment regimen or the method of treatment according to embodiment 10, wherein the PD-1 axis antagonist is PD-L1 antagonist is selected from the group consisting of avelumab, BMS-936559, CA-170, durvalumab, MCLA-145, SP142, STI-A1011, STI-A1012, STI-A1010, STI-A1014 and Atezolizumab and combination thereof. [0306] Embodiment 12: The treatment regimen or the method of treatment according to embodiment 11, wherein the PD-L1 antagonist is Atezolizumab. [0307] Embodiment 13: A treatment regimen for treating small cell lung cancer (SCLC) in a subject, comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of. Atezolizumab. [0308] Embodiment 14: A method of treating small cell lung cancer in a subject, the method comprising administering to the subject, , an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab. [0309] Embodiment 15: A method of enhancing an immune response in a subject suffering from small cell lung cancer, the method comprising administering to the subject a regimen comprising, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab Attorney Reference: ONKO-003/01WO [0310] Embodiment 16: A method of enhancing an innate immune response in a subject afflicted with small cell lung cancer , the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab, wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0311] Embodiment 17: A method of enhancing an innate immune response in a subject with small cell lung cancer (SCLC), the method comprising administering to the subject, , an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab, wherein the enhanced innate immune response is associated with suppression of T- regulatory cells. [0312] Embodiment 18: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with small cell lung cancer (e.g. ES-SCLC), the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. [0313] Embodiment 19: A method of enhancing immune function in a subject afflicted with small cell lung cancer (SCLC), the method comprising administering to the subject effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. [0314] Embodiment 20: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. [0315] Embodiment 21: A method for reducing the toxicity of Talabostat with a lower effective dose of Talabostat, the method comprising administering to a subject afflicted with small cell lung cancer (SCLC), effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. [0316] Embodiment 22: The treatment regimen or the method of treatment according to any of Embodiments 13-21, wherein the Talabostat or the pharmaceutically acceptable salt thereof and Attorney Reference: ONKO-003/01WO the Atezolizumab are administered to the subject in one or more (e.g. 1, 2, 3, 4, 5, 6 or more) treatment cycles, where each treatment cycle is of about 21 days duration. [0317] Embodiment 23: The treatment regimen or the method of treatment according to any of Embodiments 122, wherein after cessation of treatment the subject maintains a sustained response to progression of the small cell lung cancer. [0318] Embodiment 24: The treatment regimen or the method of treatment according to Embodiment 22 or 23, wherein for each treatment cycle the Talabostat or the pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1. [0319] Embodiment 25: The treatment regimen or the method of treatment according to any of Embodiments 1-24, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered orally (e.g. as a tablet formulation). [0320] Embodiment 26: The treatment regimen or the method of treatment according to any of Embodiments 13-24, wherein the Atezolizumab is administered by injection (e.g. intravenously). [0321] Embodiment 27: The treatment regimen or the method of treatment according to any of Embodiments 1-26, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.001 mg/kg to about 0.1 mg/kg (e.g. about 0.001 mg/kg to about 0.035 mg/kg, or about 0.001 mg/kg to about 0.014 mg/kg). [0322] Embodiment 28: The treatment regimen or the method of treatment according to any of Embodiments 13-27, wherein the Atezolizumab is administered at a dose of from about 1 mg/kg to about 20 mg/kg per day. [0323] Embodiment 29: The treatment regimen or the method of treatment according to any of Embodiments 1-28, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.4 mg to about 0.6 mg (e.g. administered orally twice daily, such as at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening). Attorney Reference: ONKO-003/01WO [0324] Embodiment 30: The treatment regimen or the method of treatment according to any of Embodiments 13-28, wherein about 0.2 mg twice daily dose of the Talabostat or the pharmaceutically acceptable salt thereof is administered on one or more days of a treatment cycle with an effective amount of the Atezolizumab on day 1 of the treatment cycle. [0325] Embodiment 31: The treatment regimen or the method of treatment according to any of Embodiments 13-28, wherein about 0.2 mg twice daily dose of the Talabostat or the pharmaceutically acceptable salt thereof is administered on one or more days of a treatment cycle with an effective amount of the Atezolizumab on day 1 of the treatment cycle. [0326] Embodiment 32: A treatment regimen for treating SCLC in a subject, comprising administering to the subject, about 0.3 mg twice daily dose of Talabostat or a pharmaceutically acceptable salt thereof on one or more days of a treatment cycle and an effective amount of Atezolizumab on day 1 of the treatment cycle. [0327] Embodiment 33: A method of treating SCLC in a subject, comprising administering Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0328] Embodiment 34: A method of enhancing an immune response in a subject suffering from SCLC, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0329] Embodiment 35: A method of enhancing an innate immune response in a subject afflicted with SCLC the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and , Attorney Reference: ONKO-003/01WO wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0330] Embodiment 36: A method of enhancing an innate immune response in a subject with SCLC, the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and , wherein the enhanced innate immune response is associated with suppression of T-regulatory cells [0331] Embodiment 37: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with SCLC, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0332] Embodiment 38: A method of enhancing immune function in a subject afflicted with small cell lung cancer, the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0333] Embodiment 39: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with SCLC, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0334] Embodiment 40: A method for reducing the treatment related adverse effects (TRAEs) in a subject afflicted with SCLC, comprising administering Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Atezolizumab, Attorney Reference: ONKO-003/01WO wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0335] Embodiment 41: The treatment regimen or the method of treatment according to any of Embodiments 13-40, wherein the Atezolizumab is administered at a total dose of from about 500 mg to about 1500 mg per day (e.g. about 1200 mg per day). [0336] Embodiment 42: The treatment regimen or the method of treatment according to any of Embodiments 1-41, wherein the total daily dose of Talabostat or the pharmaceutically acceptable salt thereof in cycle 1 is lower than the total daily dose of the Talabostat or the pharmaceutically acceptable salt thereof in one or more subsequent cycles. [0337] Embodiment 43: The treatment regimen or the method of treatment according to any of Embodiments 1-42, comprising administering Talabostat mesylate. [0338] Embodiment 44: The treatment regimen or the method according to any of Embodiments 1 to 43, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily for one or more consecutive days beginning on day 1 of the first treatment cycle. [0339] Embodiment 45: The treatment regimen or the method according to any of Embodiments 1 to 44, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8-14 of the first treatment cycle. [0340] Embodiment 46: The treatment regimen or the method according to any of Embodiments 1 to 45, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on days 1-3 of the first treatment cycle followed by rest period (day 4 to7) and then about 0.3 mg twice daily (on days 8-11) of the first treatment cycle. [0341] Embodiment 47: A treatment regimen for treating small cell lung cancer (SCLC) in a subject , the regimen comprising administering to the subject Talabostat mesylate and Atezolizumab in one or more treatment cycles, where each treatment cycle is of about 21 days Attorney Reference: ONKO-003/01WO duration, and for each treatment cycle the Talabostat is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1, wherein the Talabostat mesylate is administered as one or more tablets to provide a total daily dose of the Talabostat of from about 0.4 mg to about 0.6 mg and the Atezolizumab is administered as a single intravenous injection to provide a dose of from about 500 mg to about 1500 mg per day. [0342] Embodiment 48: The treatment regimen or the method according to any of Embodiments 1 to 47, wherein the Small Cell Lung Cancer is locally advanced or metastatic. [0343] Embodiment 49: The treatment regimen or the method according to any of Embodiments 1 to 48, wherein the subject experiences no TRAEs. [0344] Embodiment 50: The treatment regimen or the method according to embodiment 49, the TRAE are one or more of hypotension, dizziness, headache, syncope, dyspnea, chills, pyrexia, malaise, weakness, edema/peripheral swelling, hypovolemia, hypothermia, fatigue, nausea, vomiting, diaphoresis, flushing, migraine, diarrhea, constipation, alopecia, pharyngitis, chest pain, anorexia, weight increase, weight decrease, vertigo, syncope, conjunctivitis, blurred vision, pallor, pruritus, rash, fungal vaginosis, hyperglycemia, hyperkalemia, hypokalemia, hoarseness, dyspnea, anoxia, deep venous thrombosis, upper respiratory infection, blood in stool, dizziness, rigors, sepsis, pain, hypereosinophilia, dehydration, electrolyte imbalance, arthralgia, rhabdomyolysis, myalgia, constipation, hypocalcemia, neutropenia, febrile neutropenia, anemia, leukopenia, pancytopenia, and lymphopenia, somnolence, insomnia, epistaxis, dyspepsia, dysgeusia, thrombocytopenia, cyanosis peripheral, hypovolemic shock, respiratory failure, cough, pneumonitis, cardiac tamponade, acidosis, renal failure and cardiac arrest. [0345] Embodiment 51: The treatment regimen or the method according to any of preceding Embodiments, wherein the subject achieves a stable disease response or better, as measured by RECIST 1.1. [0346] Embodiment 52: The treatment regimen or the method according to any of preceding Embodiments, wherein the subject achieves a partial response or better, as measured by RECIST 1.1. Attorney Reference: ONKO-003/01WO [0347] Embodiments 53: The treatment regimen or the method of any of the preceding embodiments, wherein the subject achieves a complete response, as measured by RECIST 1.1. [0348] Embodiment 54: The treatment regimen or the method according to any of preceding embodiments, wherein the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg once daily dose of Talabostat. [0349] Embodiment 55: The treatment regimen or the method according to any of preceding embodiments, wherein the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg once daily dose of Talabostat. [0350] Embodiment 56: The treatment regimen or the method according to Embodiment 43, wherein the maximum increase in cytokines is observed at day 14 of continuous dosing. [0351] Embodiment 57: The treatment regimen or the method according to any of Embodiments 22 to 56, wherein the subject is not previously treated with PD-1/PD-L1 or CTLA- 4 antibodies. [0352] Embodiment 58: The treatment regimen or the method according to any of Embodiments 22 to 27, wherein the subject has relapsed or progressed with PD-1/PD-L1 or CTLA- 4 antibodies. [0353] Embodiment 59: The treatment regimen or the method of treatment according to any of Embodiments 1-58, comprising administering Talabostat mesylate. [0354] Embodiment 60: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject is 18 years of age or older. [0355] Embodiment 61: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject has a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). [0356] Embodiment 62: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject has an Eastern Cooperative Oncology Group performance status of 0 or 1. Attorney Reference: ONKO-003/01WO [0357] Embodiment 63: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the Atezolizumab is administered at a dose of 1,200 mg as an LQWUDYHQRXV^^,9^^LQIXVLRQ^RYHU^^^^^^PLQXWHV^RQ^GD\^^^RI^HDFK^F\FOH^^L^H^^^HYHU\^^^ZHHNV^^ [0358] Embodiment 64: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the small cell lung cancer (SCLC) is extensive stage SCLC. [0359] Embodiment 65: A treatment regimen for treating pancreatic cancer in a subject, the treatment regimen comprising administering to the subject, as an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0360] Embodiment 66: A method of treating pancreatic cancer in a subject, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0361] Embodiment 67: A method of enhancing an immune response in a subject suffering from pancreatic cancer, the method comprising administering to the subject a regimen comprising, as separate pharmaceutical formulations, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist. [0362] Embodiment 68: A method of enhancing an innate immune response in a subject with pancreatic cancer, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist., wherein the enhanced innate immune response is associated with suppression of T- regulatory cells. [0363] Embodiment 69: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0364] Embodiment 70: A method of enhancing immune function in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. Attorney Reference: ONKO-003/01WO [0365] Embodiment 71: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0366] Embodiment 72: A method for reducing the toxicity of Talabostat with a lower effective dose of Talabostat, the method comprising administering to a subject afflicted with pancreatic cancer, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and PD-1 axis antagonist. [0367] Embodiment 73: The treatment regimen or the method of treatment according to any of Embodiments 65-72, wherein the PD-1 axis antagonist includes PD1 antagonist (for example anti-PD-1 antibody), PD-Ll antagonist (for example anti-PD-Ll antibody) and PD-L2 antagonist (for example anti-PD-L2 antibody). [0368] Embodiment 74: The treatment regimen or the method of treatment according to any of Embodiments 65-72, wherein the PD-1 axis antagonist is PD1 antagonist selected from the group consisting of, BGB-A317, Pembrolizumab, MEDI0680, Nivolumab, PDR001, PF- 06801591, REGN-2810, SHR-1210, , TSR-042, and combination thereof [0369] Embodiment 75: The treatment regimen or the method of treatment according to embodiment 73 or 74, wherein PD1 antagonist is Pembrolizumab. [0370] Embodiment 76: A treatment regimen for treating pancreatic cancer in a subject, the treatment regimen comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab. [0371] Embodiment 77: A method of treating pancreatic cancer in a subject, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab. [0372] Embodiment 78: A method of enhancing an immune response in a subject suffering from pancreatic cancer, the method comprising administering to the subject a regimen comprising, Attorney Reference: ONKO-003/01WO an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab. [0373] Embodiment 79: A method of enhancing an innate immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab, wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0374] Embodiment 80: A method of enhancing an innate immune response in a subject with pancreatic cancer, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab, wherein the enhanced innate immune response is associated with suppression of T-regulatory cells [0375] Embodiment 81: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with pancreatic cancer, the method comprising administering to the subject effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. [0376] Embodiment 82: A method of enhancing immune function in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, , effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. [0377] Embodiment 83: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. [0378] Embodiment 84: A method for reducing the toxicity of Talabostat with a lower effective dose of Talabostat, the method comprising administering to a subject afflicted with pancreatic cancer, effective amounts of the Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. Attorney Reference: ONKO-003/01WO [0379] Embodiment 85: The treatment regimen or the method of treatment according to any of Embodiments 52-61, wherein the Talabostat or the pharmaceutically acceptable salt thereof and Pembrolizumab are administered to the subject in one or more (e.g. 1, 2, 3, 4, 5, 6 or more) treatment cycles, where each treatment cycle is of about 21 days duration. [0380] Embodiment 86: The treatment regimen or the method of treatment according to any of Embodiments 76-85, wherein after cessation of treatment the subject maintains a sustained response to progression of pancreatic cancer. [0381] Embodiment 87: The treatment regimen or the method of treatment according to Embodiment 85 or 86, wherein for each treatment cycle the Talabostat or thepharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Pembrolizumab is administered on day 1. [0382] Embodiment 88: The treatment regimen or the method of treatment according to any of Embodiments 76-87, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered orally (e.g. as a tablet formulation). [0383] Embodiment 89: The treatment regimen or the method of treatment according to any of Embodiments 76-87 wherein the Pembrolizumab is administered by injection (e.g. intravenously). [0384] Embodiment 90: The treatment regimen or the method of treatment according to any of Embodiments 76-89, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.001 mg/kg to about 0.1 mg/kg (e.g. about 0.001 mg/kg to about 0.035 mg/kg, or about 0.001 mg/kg to about 0.014 mg/kg). [0385] Embodiment 91: The treatment regimen or the method of treatment according to any of Embodiments 76-90, wherein the Pembrolizumab is administered at a dose of from about 1 mg/kg to about 20 mg/kg per day. [0386] Embodiment 92: The treatment regimen or the method of treatment according to any of Embodiments 76-91 wherein the Talabostat or the pharmaceutically acceptable salt thereof is Attorney Reference: ONKO-003/01WO administered at a total daily dose of from about 0.4 mg to about 0.6 mg (e.g. administered orally twice daily, such as at a dose of about 0.4 mg in the morning and about 0.2 mg in the evening). [0387] Embodiment 93: The treatment regimen or the method of treatment according to any of Embodiments76-91, wherein about 0.2 mg twice daily dose of the Talabostat or the pharmaceutically acceptable salt thereof is administered on one or more days of a treatment cycle with an effective amount of the Pembrolizumab on day 1 of the treatment cycle. [0388] Embodiment 94: The treatment regimen or the method of treatment according to any of Embodiments 76-91, wherein about 0.2 mg twice daily dose of the Talabostat or the pharmaceutically acceptable salt thereof is administered on one or more days of a treatment cycle with an effective amount of the Pembrolizumab on day 1 of the treatment cycle. [0389] Embodiment 95: A treatment regimen for treating pancreatic cancer in a subject , the treatment regimen comprising administering to the subject, about 0.3 mg twice daily dose of Talabostat or a pharmaceutically acceptable salt thereof on one or more days of a treatment cycle and an effective amount of Pembrolizumab on day 1 of the treatment cycle. [0390] Embodiment 96: A method of treating pancreatic cancer in a subject, comprising administering Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0391] Embodiment 97: A method of enhancing an immune response in a subject suffering from pancreatic cancer, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0392] Embodiment 98: A method of enhancing an innate immune response in a subject afflicted with pancreatic cancer the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective Attorney Reference: ONKO-003/01WO amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and , wherein the enhanced innate immune response is associated with increased tumoricidal natural killer cells and macrophages, as well as the activity of NK cells and CD8+ T cells. [0393] Embodiment 99: A method of enhancing an innate immune response in a subject with pancreatic cancer, the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle and , wherein the enhanced innate immune response is associated with suppression of T-regulatory cells [0394] Embodiment 100: A method for treating, delaying progression or preventing or delaying tumor recurrence, tumor growth or spread of tumor in a subject afflicted with pancreatic cancer, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0395] Embodiment 101: A method of enhancing immune function in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0396] Embodiment 102: A method for initiating, sustaining or enhancing an anti-tumor immune response in a subject afflicted with pancreatic cancer, the method comprising administering to the subject Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. Attorney Reference: ONKO-003/01WO [0397] Embodiment 103: A method for reducing the treatment related adverse effects (TRAEs) in a subject afflicted with pancreatic cancer, comprising administering Talabostat or a pharmaceutically acceptable salt thereof in combination with a therapeutically effective amount of Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a dose of about 0.3 mg twice daily on one or more days of a treatment cycle. [0398] Embodiment 104: The treatment regimen or the method of treatment according to any of Embodiments 76-103, wherein the Pembrolizumab is administered at a total dose of from about 100 mg to about 500 mg per day (e.g. about 200 mg per day). [0399] Embodiment 105: The treatment regimen or the method of treatment according to any of Embodiments 76-104, wherein the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in cycle 1 is lower than the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in one or more subsequent cycles. [0400] Embodiment 106: The treatment regimen or the method of treatment according to any of Embodiments 76-105, comprising administering Talabostat mesylate. [0401] Embodiment 107: The treatment regimen or the method according to any of Embodiments76 to 106, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily for one or more consecutive days beginning on day 1 of the first treatment cycle. [0402] Embodiment 108: The treatment regimen or the method according to any of Embodiments 76 to 107, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8-14 of the first treatment cycle. [0403] Embodiment 109: The treatment regimen or the method according to any of Embodiments 76 to 108, wherein the subject is administered the Talabostat or the pharmaceutically acceptable salt thereof at a dose of about 0.3 mg twice daily on days 1-3 of the first treatment cycle followed by rest period (day 4 to7) and then about 0.3 mg twice daily (on days 8-11) of the first treatment cycle. Attorney Reference: ONKO-003/01WO [0404] Embodiment 110 : A treatment regimen for treating pancreatic cancer in a subject , the treatment regimen comprising administering to the subject Talabostat mesylate and Pembrolizumab in one or more treatment cycles, where each treatment cycle is of about 21 days duration, and for each treatment cycle the Talabostat is administered on each of days 1 to 14 and the Pembrolizumab is administered on day 1, wherein the Talabostat mesylate is administered as one or more tablets to provide a total daily dose of the Talabostat of from about 0.4 mg to about 0.6 mg and the Pembrolizumab is administered as a single intravenous injection to provide a dose of from about 100 mg to about 500 mg per day. [0405] Embodiment 111: The treatment regimen or the method according to any of Embodiments 76 to 110, wherein pancreatic cancer which is locally advanced or metastatic. [0406] Embodiment 112: The treatment regimen or the method according to any of Embodiments 76 to 111, wherein the subject experiences no TRAEs. [0407] Embodiment 113: The treatment regimen or the method according to embodiment 112, the TRAE are one or more of hypotension, dizziness, headache, syncope, dyspnea, chills, pyrexia, malaise, weakness, edema/peripheral swelling, hypovolemia, hypothermia, fatigue, nausea, vomiting, diaphoresis, flushing, migraine, diarrhea, constipation, alopecia, pharyngitis, chest pain, anorexia, weight increase, weight decrease, vertigo, syncope, conjunctivitis, blurred vision, pallor, pruritus, rash, fungal vaginosis, hyperglycemia, hyperkalemia, hypokalemia, hoarseness, dyspnea, anoxia, deep venous thrombosis, upper respiratory infection, blood in stool, dizziness, rigors, sepsis, pain, hypereosinophilia, dehydration, electrolyte imbalance, arthralgia, rhabdomyolysis, myalgia, constipation, hypocalcemia, neutropenia, febrile neutropenia, anemia, leukopenia, pancytopenia, and lymphopenia, somnolence, insomnia, epistaxis, dyspepsia, dysgeusia, thrombocytopenia, cyanosis peripheral, hypovolemic shock, respiratory failure, cough, pneumonitis, cardiac tamponade, acidosis, renal failure and cardiac arrest. [0408] Embodiment 114: The treatment regimen or the method according to any of preceding Embodiments, wherein the subject achieves a stable disease response or better, as measured by RECIST 1.1. Attorney Reference: ONKO-003/01WO [0409] Embodiment 115: The treatment regimen or the method according to any of preceding Embodiments, wherein the subject achieves a partial response or better, as measured by RECIST 1.1. [0410] Embodiments 116: The treatment regimen or the method of any of the preceding embodiments, wherein the subject achieves a complete response, as measured by RECIST 1.1. [0411] Embodiment 117: The treatment regimen or the method according to any of preceding embodiments, wherein the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg once daily dose of Talabostat. [0412] Embodiment 118: The treatment regimen or the method according to any of preceding embodiments, wherein the subject experiences an increase in pro-inflammatory cytokines relative to a subject that is administered a single 0.6 mg once daily dose of Talabostat. [0413] Embodiment 119: The treatment regimen or the method according to Embodiment 118, wherein the maximum increase in cytokines is observed at day 14 of continuous dosing. [0414] Embodiment 120: The treatment regimen or the method according to any of Embodiments 84to 119, wherein the subject was not previously treated with PD-1/PD-L1 or CTLA-4 antibodies. [0415] Embodiment 121: The treatment regimen or the method according to any of Embodiments 84 to 120, wherein the subject has relapsed or progressed with PD-1/PD-L1 or CTLA-4 antibodies. [0416] Embodiment 122: The treatment regimen or the method of treatment according to any of Embodiments 64-121, comprising administering Talabostat mesylate. [0417] Embodiment 123: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject is 18 years of age or older. [0418] Embodiment 124. The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject has a measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Attorney Reference: ONKO-003/01WO [0419] Embodiment 125: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the subject has an Eastern Cooperative Oncology Group performance status of 0 or 1. [0420] Embodiment 126: The treatment regimen or the method of treatment according to any of preceding embodiments, wherein the Atezolizumab is administered at a dose of 1,200 mg as DQ^LQWUDYHQRXV^^,9^^LQIXVLRQ^RYHU^^^^^^PLQXWHV^RQ^GD\^^^RI^HDFK^F\FOH^^L^H^^^HYHU\^^^ZHHNV^^ [0421] Embodiment 127: The treatment regimen or method of treatment according to any of preceding embodiments, wherein the pancreatic cancer is selected from a group comprising exocrine pancreatic cancer, pancreatic ductal carcinoma or adenocarcinoma of pancreas, squamous cell carcinoma, adenosquamous carcinoma, colloid carcinoma, pancreatic neuroendocrine tumors, cystic tumors including IPMNS, acinar cell carcinoma, intraductal papillary-mucinous neoplasm (IPMN) or mucinous cystic neoplasm with an invasive adenocarcinoma. 7. Examples [0422] Example 1: Phase 2 Single Arm Study of Talabostat mesylate, a Small Molecule Inhibitor of Dipeptidyl Peptidases (DPP), added to Atezolizumab in Patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC), as Maintenance following Treatment with Carboplatin plus Etoposide. Table 4. Study Objectives and Endpoints

Attorney Reference: ONKO-003/01WO

Duration of Treatment [0423] Patients will remain on treatment until disease progression, death, unacceptable toxicity, symptomatic deterioration, adverse event unrelated to study drug, lost to follow-up, the Investigator decides to discontinue treatment, the patient decides to discontinue treatment or withdraw consent or the company decides to terminate the trial. Treatment may continue beyond disease progression if there is clinical benefit as determined by the Investigator. Study Population Attorney Reference: ONKO-003/01WO [0424] Adults 18 years of age or older with Extensive Stage Small Cell Lung Cancer (ES- SCLC) in Maintenance following Treatment with four cycles of Carboplatin plus Etoposide and Atezolizumab. [0425] Key Inclusion Criteria 1. Must have signed and dated written ICF in accordance with regulatory and institutional guidelines. 2. Must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study. 3. Has histologically or cytologically confirmed Small Cell Lung Cancer which is locally advanced or metastatic i.e., Extensive Stage (ES-SCLC) 4. Has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST 1.1). 5. Has received 4 cycles of Carboplatin and Etoposide chemotherapy plus Atezolizumab for locally advanced or metastatic disease i.e., Extensive Stage (ES-SCLC). 6. Has recovered to CTCAE Grade 1 or baseline for all toxicities attributed to chemotherapy other than alopecia and fatigue. Participants with toxicities attributed to prior anti-cancer therapy that are not expected to resolve and result in long-lasting sequelae, such as neuropathy after platinum-based therapy or endocrinopathy managed with replacement therapy, are permitted to enroll. 7. Has an Eastern Cooperative Oncology Group performance status of 0 or 1. 8. Has a documented left ventricular ejection fraction > 45% using standard echocardiogram or multigated acquisition scan test at Screening. 9. Has adequate organ function within 28 days of treatment initiation. 10. +DV^R[\JHQ^VDWXUDWLRQ^^^^^^^RQ^URRP^DLU^^ Attorney Reference: ONKO-003/01WO 11. 3DWLHQWV^ ZLWK^ K\SHUWHQVLRQ^ PXVW^ EH^ RQ^ ^^ ^^ DQWLK\SHUWHQVLYH^ PHGLFDWLRQV^ DQG^ ZLWKRXW^ change for the 14 days prior to randomization. Screening blood pressure must be systolic < 150 mm Hg and < 90 mm Hg for diastolic blood pressure. 12. Patients with brain metastases are eligible if all the criteria below are fulfilled: a) Brain metastases must be treated at least 2 weeks prior to enrollment. b) Brain imaging after treatment and within the screening period must demonstrate no new or progressing brain metastases. c) No requirement for systemic corticosteroids > 10 mg/day prednisone equivalents. Stable doses of anticonvulsants are allowed. d) No clinically significant symptoms associated with brain metastases. Key Exclusion Criteria [0426] A patient will be excluded from this study if he/she meets any of the following criteria: 1. Has received >1 prior cytotoxic chemotherapy regimens other than Carboplatin and Etoposide chemotherapy for Small Cell Lung Cancer which is locally advanced or metastatic i.e., Extensive Stage (ES-SCLC) 2. Has received any systemic or local immunotherapy for cancer, other than Atezolizumab 3. Has any dysphagia, odynophagia, esophageal dysmotility or stricture, known GI malabsorption syndrome, or intractable diarrhea that may significantly alter the absorption of an orally administered study drug; or has a known history of immune colitis or inflammatory bowel disease. 4. Has prolonged Fridericia’s corrected QT interval (QTcF) > 450 ms for men and > 470 ms for women at Screening. 5. Has known cardiovascular history, including unstable or deteriorating disease within 12 months prior to screening including but not limited to: Attorney Reference: ONKO-003/01WO a) Unstable angina or myocardial infarction. b) Transient ischemic attack (TIA)/Cerebrovascular accident (CVA). c) Congestive heart failure (New York Heart Association [NYHA] Class III or IV). d) Uncontrolled clinically significant arrhythmias. 6. Has a history of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA/TIA arterial thromboembolic event (e.g., internal jugular vein thrombosis) within 3 months prior to Cycle 1 Day 1. 7. Partial thromboplastin time (PTT) > 1.5 × ULN of the institution’s normal range and INR (international normalized ratio) > 1.5 × ULN. Patients on anticoagulants (such as warfarin) will be permitted to enroll if the INR is in the acceptable therapeutic range (< 1.5 × ULN). 8. Has persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, HRVLQRSKLOLD^^RU^UHFHQW^ZHLJKW^ORVV^RI^^^10%. 9. Has a history of symptomatic orthostatic hypotension within 3 months prior to enrollment. Orthostatic hypotension is defined as a drop in systolic blood pressure (BP) of ^^^^^PP+J^RU^GLDVWROLF^%3^RI^^^^^^PP+J^ 10. Women who are pregnant, lactating, or intending to become pregnant during the study 11. Treatment with systemic immunosuppressive medications (including, but not limited to prednisone, within 2 weeks prior to enrollment. Number of Patients (Planned): [0427] Safety run-inn Phase: approximately six (6) to twelve (12) patients. Phase 2: approximately thirty (30) patients. Total: 36 to 42 patients Attorney Reference: ONKO-003/01WO Number of Study Sites: [0428] Ten (10) to twelve (12) study centers in the US are planned. Study Design [0429] This is an open-label, single arm, Phase 2, multicenter study with a 3 + 3 safety run-in phase to determine the safety and efficacy of Talabostat administered orally in combination Atezolizumab administered IV as maintenance following completion of 4 cycles of Carboplatin plus Etoposide and Atezolizumab in patients with Extensive Stage Small Cell Lung Cancer (ES- SCLC). [0430] During the safety run-in phase, the safety and tolerability of the doses of Talabostat in combination with Atezolizumab (1,200 mg every 3 weeks) will be assessed and the Recommended Phase 2 Dose (RP2D) will be determined in patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) in maintenance. [0431] Initially, three patients will be enrolled sequentially i.e., first patient should complete the 30 days DLT assessment period without DLT; the second and third patient may then be enrolled and observed for 30 days.. If no protocol defined DLTs are observed, dose maybe escalated. In the event of a DLT more patients will be treated sequentially and observed for DLTs as described below. [0432] The patients will be treated with the starting dose of Talabostat 0.4 mg (0.2mg BID days 1-14, every 3 weeks) and 1,200 mg Atezolizumab once on day 1 every 21 days. A DLT (see DLT definitions) observation period of 30 days will follow. [0433] If “0” DLTs are observed in the first three patients during the 30 days immediately after administration of the combination-DLT observation period, dose will be escalated to the second cohort with 0.6 mg talabostat (0.2 mg BID days 1-7 and 0.3 mg BID days 8-14 in cycle 1) followed by talabostat 0.3 mg BID days 1-14 every 21 days thereafter. If “0” DLTs are observed in the first 3 patients during the DLT observation period this will be the RP2D for the combination to be confirmed and documented by the Safety Review Committee (SRC) and the Safety run in period can be considered complete.. [0434] If 1 DLTs is observed in the first three patients treated, during the DLT observation period, 3 additional patients will be enrolled in that cohort and observed for 30 days. If no additional patients experience DLTs and only 1 in 6 patients has a DLT, dose will be escalated to the second cohort with 0.6 mg talabostat (0.3 mg BID days 1-7 and 0.3 mg BID days 8-14). DLT assessment will follow the same process as conducted in the prior cohort for the determination of RP2D. Attorney Reference: ONKO-003/01WO [0435] ,I^^^^^'/7V^are observed in the first 3 patients during DLT observation period, , an additional 3 patients will be enrolled in that cohort. If more than 2 from 6 patients has a DLT, the Recommended Phase 2 Dose (RP2D) will be 0.4 mg/day Talabostat (0.2mg BID days 1-14) plus 1,200 mg Atezolizumab every 21 days i.e., Cycle; to be confirmed and documented by the Safety Review Committee (SRC). [0436] In the Phase 2-part patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) will receive Talabostat at the RP2D in combination with 1,200 mg of Atezolizumab. [0437] A Safety Review Committee (SRC), which will be comprised of both investigators and sponsor representatives, will review the safety during the Safety run-inn part of the study before the Phase 2 components begin. If an intermediate dose is selected at the end of Safety run-in part, the committee will monitor the first 6 Phase 2 patients through 3 weeks (Cycle 1). [0438] All safety data from all patients enrolled in first dose cohort (0.2mg BID days 1-14) will be reviewed to confirm any DLTs that were experienced and to determine enrolling the second cohort (0.2 mg BID days 1-7 then 0.3mg BID days 8-14 in cycle 1), as well as the Talabostat dosing regimen to be used in the Phase 2 portions. [0439] Unless doses were held because of adverse events (AEs), a patient must have received >70% of planned Talabostat doses in Cycle 1 (e.g., >10 of 14 planned doses) with Atezolizumab dosed on Day 1 of Cycle 1 to be eligible for DLT assessment. [0440] Eligible patients will receive Talabostat on Days 1 to 14 of a 21-day cycle (depending the dose selected in the safety run-in phase) plus Atezolizumab 1,200 mg administered IV on Day l of every 2 l days. [0441] Across all study phases, patients will be screened for study eligibility within 28 days before the first study drug dose after provision of written informed consent. Patients who are determined to be eligible, based on Screening assessments, will be enrolled in the study on Cycle (C)1, Day (D) l (baseline, before the first dose of Talabostat). [0442] During treatment, patients will attend study center visits and have study evaluations performed as detailed in the Schedule of Assessments (Table 5). All study visits will be conducted on an outpatient basis but may be conducted on an inpatient basis per the investigator's judgement. [0443] Patients may continue to receive treatment until the development of radiographic progression by RECIST v1.1 criteria, unequivocal clinical progression, unacceptable toxicity, Attorney Reference: ONKO-003/01WO another discontinuation criterion is met, or closure of the study; no maximum duration of therapy has been set. [0444] Treatment may continue beyond the first radiographic progression if there is clinical benefit. Criteria for Continuing Treatment in the Presence of Increased Radiographic Tumor Size [0445] Radiographic Progression per RECIST v1.1 Patients must provide written consent Treatment may be continued provided: Evidence of clinical benefit as assessed by investigator No signs/symptoms indicating unequivocal disease progression No decline in ECOG PS attributed to disease progression No tumor growth at critical sites Patients acknowledge deferring alternative therapies via ICF Continue treatment until evidence of persistent radiographic disease progression, symptomatic deterioration due to disease progression, or unacceptable toxicity. [0446] Talabostat dose reduction modifications within a treatment cycle will be at the discretion of the investigator. Doses should be taken at approximately the same time every day. Talabostat should not be taken on an empty stomach. Doses held because of AEs should not be made up on subsequent days within or following a cycle. A dose that is missed for reasons other than an AE (e.g., the patient forgets to take a dose) may be taken at least 6 hours prior to the next planned dose; otherwise, the missed dose may be administered on a day subsequent to a scheduled dose. Any additional adjustments should be discussed with the medical monitor or designee. If a dose is vomited within approximately 10 minutes of dosing, the patient may be re-dosed. 1f the patient vomits >10 minutes after dosing, no further attempts at dosing that particular dose should take Attorney Reference: ONKO-003/01WO place; dosing should resume with the next dose. Under no circumstances should missed doses be made-up when the patient is already taking a planned dose (i.e., no “doubling-up” to account for missed doses). [0447] Patients will complete an End of Treatment (EOT) visit upon discontinuation of the study treatment, within 2l days after their last dose of study drug. Upon discontinuation of study treatment, Safety Follow-Up is to be conducted 30 days (7 days) after their last dose of protocol therapy as well as at additional subsequent time points if drug-related AEs have not yet resolved. [0448] Patients will also be contacted by telephone approximately every 90 days for clinical evidence of progressive disease (PD) in settings in which discontinuation of study therapy was for reasons other than PD (tumor measurements as specified in the protocol are not required after the EOT visit), and for assessment of survival status. [0449] This extended follow-up for disease status and survival after discontinuation of study treatment will continue for up to 12 months after study treatment is discontinued to assess the Overall Survival (OS). [0450] Safety will be assessed during the study by documentation of AEs, clinical laboratory tests, physical examination, vital sign measurements, and Eastern Cooperative Oncology Group (ECOG) performance status. [0451] All patients must have pre-treatment (prior to study treatment dosing) imaging (computed tomography [CT] scan of chest/abdomen/pelvis or magnetic resonance imaging [MRI] for baseline tumor measurements, as well as bone scintigraphy [BS]). Patients with skin, subcutaneous, or lymph node metastases may also have tumor evaluations (including measurements, with a ruler) by means of physical examination. [0452] Patients with a history of central nervous system (CNS) malignant involvement or CNS symptoms should have either CT or MR1 imaging of the brain performed to assess active CNS malignancy. [0453] Tumor measurements and disease response assessments (CT or MRI; BS) are also to be performed at the end of Cycle 3 (approximately 9 weeks after the first study treatment dose), and then approximately every 9 weeks thereafter until development of PD. Test Product, Dose and Mode of Administration Attorney Reference: ONKO-003/01WO [0454] Talabostat administered as oral tablets at an assigned dose: [0455] Safety run-inn Phase at dose of 0.2 mg, or 0.3 mg administered twice daily (BID) days 1- 14 of a 21-day cycle. [0456] Phase 2 at RP2D. [0457] Atezolizumab administered at a dose of 1,200 mg as an intravenous (IV) infusion RYHU^^^^^^PLQXWHV^RQ^GD\^^^RI^HDFK^F\FOH^^L^H^^^HYHU\^^^ZHHNV^^ Pharmacokinetic Evaluation [0458] Blood samples for PK analyses of Talabostat, its metabolites, will be collected as summarized in Error! Reference source not found.6. Plasma concentrations of Talabostat and its metabolites, will be measured for each PK sample using validated or qualified method(s). [0459] PK parameters such as maximum concentration (C_max), time to C_max (T_max), area under the curve (AUC), clearance, and half-life (t_1/2) will be estimated from plasma or serum concentration- time data where possible. Pharmacodynamic Evaluation: [0460] Baseline and on-treatment blood biomarkers will be assessed in selected blood and serum samples collected for biomarkers (Refer to Table 5) Immunogenicity Evaluation: [0461] Serum samples for the assessment of anti-drug antibodies related to Atezolizumab will be collected prior to infusions XX (and 12; and every 6 infusions thereafter and the EOT visit. Response Evaluation [0462] Response and progression will be determined by local radiology review using RECIST 1.1 and/or iRECIST when possible. Patients will be assessed for response by CT or MRI until progression or treatment discontinuation, whichever occurs later. Attorney Reference: ONKO-003/01WO [0463] The primary efficacy parameter is the objective response rate (ORR) defined as the proportion of response evaluable patients in Phase 2 achieving a confirmed PR or CR as best response by RECIST 1.1. [0464] The secondary efficacy parameters of best overall response (BOR) of CR, PR, SD, and PD; time to response (TTR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) will also be assessed. Evaluation of Dose-Limiting Toxicity (Safety Run-In Phase) [0465] Standard 3 + 3 sequential patients, guided by the emergence or non-emergence of dose-limiting toxicities (DLTs), will be applied. [0466] Any of the following drug related AEs (occurring in Cycle 1, Day 1 through Day 30) will be considered a DLT: Grade 4 neutropenia (ANC < 500 cells/mm3) regardless of duration. *UDGH^^^^^QHXWURSHQLD^ZLWK^IHYHU^^RUDO^WHPSHUDWXUH^^^^^^^^&^^DQG^RU^LQIHFWLRQ^ Grade 4 thrombocytopenia (platelets < 25,000/mm3) lasting more than 7 days. *UDGH^^^^^WKURPERF\WRSHQLD^ZLWK^FOLQLFDOO\^PHDQLQJIXO^EOHHGLQJ^DW^DQ\^WLPH^ Grade 4 anemia. Laboratory criteria meeting Hy’s Law (AST or ALT > 3 × institutional ULN with concomitant total bilirubin > 2 × ULN) in absence of other etiology (e.g., obstruction). *UDGH^^^^^LQIXVLRQ^WR[LFLW\^ $Q\^ *UDGH^ ^^^ GUXJ-related hypotension lasting > 48 hours post-dose, cytokine release syndrome, capillary leak syndrome, pulmonary edema, or symptomatic hyper eosinophilic syndrome. *UDGH^ ^^ ^^ QDXVHD^ DQG^RU^ HPHVLV^ WKDW^ RFFXUV^ IRU^ !^ ^^^ KRXUV^ GHVSLWH^ RSWLPDO^ DQWL-emetic prophylaxis (includes the use of 5 HT3 antagonists). *UDGH^^^^^GLDrrhea for > 72 hours that occurs despite optimal supportive care measures. Grade 4 diarrhea and vomiting irrespective of duration. Attorney Reference: ONKO-003/01WO &\WRNLQH^UHOHDVH^V\QGURPH^*UDGH^^^^^SHU^1&,^&7&$(^9HUVLRQ^^^ *UDGH^^^^^WXPRU^O\VLV^V\QGURPH^ $Q\^RWKHU^*UDGH^^^ ^^ QRQKHPDWRORJic toxicity that does not resolve to Grade 1 or baseline within 7 days $Q\^WR[LFLW\^UHVXOWLQJ^LQ^^^^^^^KHOG^VNLSSHG^GRVHV^RI^7DODERVWDW^GXULQJ^&\FOH^^^ Inability to start the next dose of therapy due to > 4 weeks treatment delay because of a lack of adequate recovery of study drug related hematologic/nonhematologic toxicities. [0467] $Q\^RWKHU^VWXG\^GUXJ^UHODWHG^*UDGH^^^^^QRQKHPDWRORJLF^WR[LFLWLHV^WKDW^^LQ^WKH^RSLQLRQ^RI^ the Investigator, requires a dose reduction or discontinuation of therapy. [0468] Statistical Methods [0469] The study will have a Safety Run-in part stage design, whereby 6-12 patients will be accrued, and the onset of DLTs will be assessed two cohorts i.e., 0.4 and 0.6 mg daily for 14 days. The selected RDP2 will be the one that show no more than 2 DLTs.

^U _F ^btⁱ ^T _si _L V O _n ^{a l}l_{i e} ^{h e} _h ^b ^W ₁ ^d ⁰ _n ^w _t _/ ^{a h f t} o_r ^{o y} t _t tⁱ ^e _{f si} ^v ³ _{; c} ^{i t} _{r i} ^a ₀ ^e _h ^a ⁰ _{- g} ^a _p ⁿ _{o S} ^U _F O _t w s , K ^t ₎ C _n ^m ⁿ _i ^ll - _{i Ta} N _x ^e _R _n ^S _{( n} ^{w t} ^{u C O i} _s _E ⁱ X X X ^O _{e r R v} _: ^e ^e _e ^y _t ^S _c ^{h t tt} ⁿ _i ^e _{f e s} _e ^o _t ^r _e ^d m ^{a h} _t ^y ₁ ² ^f _e ^{e m} _S _{o e} ,_{t a -} ⁴ ^h _t ^r _a D ₁ _{e c} ^{o C p} ^R ^y _{r g} ⁿ _i ^y _e ^p w ^{n l} _l ^e _i ⁿ _{r i} ^v _i ^{r -} u_n ^u _{S a 8} Y D ^{o w} _e R^d _r _y At_t ^{y y y} _t ^t _e D ^y _f A _d ^u _t ^{e f} _{1 a 1} X X X t_s ₂ _e ^s _a ^h _P _e ^h T^. _s T_L D ² ⁿ _a ^h _t _e ^r _o m o ⁿ w^o _h ^s ^t _a ^h _t

^. _d _e ^e _e n _u _o ^{r h} _n _{c t} ^{o I} ^f _{p .} ^c ^{s n} _y ⁿ _i _i ^{g C} ₍ ⁿ ₈ _e ² - ¹ - X X X X X X X X e ^c ^h _{a o} _{t e} ^t _r ^d ^a _{n e} a^{b s e} s_{k r} e^{c y} _a _{e S} D e ^b ^{b l} _p ^s _r ^t _n ^{e w} ^{l l} ^l _{i n} _i ^{w n} _i ^o _{t n} w _s ^{t -} _n ^a _g ^{o 3} p ^h _g 2 _n _P ^{e e u i} r t_s ^{e m} _o ^u _{o s} ^t _n ^ai _r D _i ^t _e _a ^t _ti ^y _t ^e _v ^{n c r} i ² _h ^{t e} _v ^d _o ^e ^{i c t} _i ^r _e _R ^p m _f ^e _s ^{t E} _r s ^s d ⁾ ^e _{t 0} c^{3 m a} o_{S h} ^t _s _{e o} ^a _n ^f ^b _h ^ei _o ^e _P ^y t_{e a C n} _{e (} ^{l /} _e D _d ^t _n ^o ^o _i ^t _a l^{C h} _t ^{f P} e ^a _u ^r _{u y n} _e ^y ^s _tr ⁱ w^e _{g o} ^h _p _t ^d _e ^{d d} _u ^e _i _s ^s _u ^l _y ^{r n} _{i h} A e _h ^t _i ⁿ ^v _i ^r _d ^e ₂ _{s e} ^r _e ^{s h} _e _c ^c _o ^{t n} ^r _{S o c} C^x _o ^t m E_si ^a _{x f} ^s G h_l ^a _{e u i} ^r _o ^f _a ^{h S} _P ^{d /} _n ^{H E} _{n S} U T ^] _n ^{R D} _{p e} ₀ ^{o b} _P ^. _{5 e} ^o _i ^l _a ^l _a ^g _i ^{P M} _/ 7 i_t ^y 4 ⁱ _t ^] ^e ₁ ^m ⁷ _o ^{c y} ⁰ _{d d 6} ^t _e ^{l m} _r ^{s c} ^o _u ^l _i ^c ^d _i ^{s S} _l G a O _g O G H [ ^d _f _a ^a ₄ _S ⁰ _[ ^e _b ^ut _s _s ^ri _b _f ^a _{f c e y} _T ⁿ _I ⁿ _I M ^h t P_i V ^C E ^C E ^C E ^U _F ^btⁱ ^T _i _LO ^W _{1 t} ⁰ _{/ f} ³ ₀ ⁰-OK N

^a ^O _{E v r e} ^t _s ^{c o n} _n _: ^{o m} ^e _{i n r} a^{ei e} l_it ⁿ _{c r} ^c ^a _o ^{o p} _i ⁿ _i _i ^{s o}i_t _c ^st ^t _ti ⁿ _{s r t} ^r ^a m _a ^e _p ^c _e ^y ₁ ^{2 a} _{t a ,} ^y _l ^f ^{n i l} _a ^c ^d _c- _{d n} s _h ^{t o} ^r _{a - t c} ⁿ _i f_I ^D _P ^l _o _{d e} ⁿ _n ^{i e} _t ^u ^a f c_e ⁿ ^f D⁴ ₁ ⁿ _e ^a _{o e} ^. _{r i} ^t _n ^l _{u o} ^p _t _t ^x _e _e ^p _{e a} ⁱ _e ⁸- ^{1 m} _i ^d _e ^c _, ^mo ^s _{o s} ^{n u o} _h ^{s s} _o ^{n r} _d ^r ^e _{t a} ^R ^{y y} _s ^{g v} _{e S a} ^y _e ^r _l ^o _E ^c _{o s} A^{y p y} _{a )} ^{s pr} _h ^{t n} _e ^c t ^r _o ⁿ D _{8 a r s} e^e _{a S} r _f ^d _{y o} o^m _e ^{) a} _{d d} ^a m^{s f} _r Y ^e _{s s} ^o A ^D _{: c} ^{n t} _{o t} ^{n t} _n ^h _{t 0} ^e ^{y 1} _{3 p} ^p _n ^e ^o _s ^s ^s _e ^st_t D ^{y y} _l ⁱ _a ^c _i ⁿ _e ^ei t _s ^m _t ^a _b ^± ₍ - s _i ^k _{d a s} _e s ^a A ₁ ² _a D _{1 a} D _n ^a ^a _{h s} ^s _{p n} ^o _{0 k s i} _i ^{9 e} _{e e} ^{b h} _t ^o t Y R _e ^c w _{E e} ^s _e ^{h t} i ^e _n A_s _d ^a _{t a} _s ^, _t ^{n y} i_r ^e w ^{b d} _{l e} ¹ v₃ ^y ,_a ^u _o ^v _a ^y ^h _a _E ^y _a ⁵ _a ^{e e n m} _r ^e _. m^h _s D V D ₁ ^w _t _{T e} ^a _{l d} ^u _e m^{e t e} _u ^g _. ^e s (_t ⁱ s_{t .} ^d ^d _l ^u ₁ _E ^r _o _T ^{f e} _r _e - _l _g ^c _n ^g ^I _d ^y ^u _d ⁿi_t ^s s j ^u _t ⁿ _{k i} ⁿ _{e o e} ^l ^{e V} _e ^t ^. m_a ^{c h} _c _{i s} ^y ^{N y b u} _{r .} ^{l s} _{o e e} ^s _s ^{d y} _C _{E a} ^{4 r} D _{1 o} ^{d e} _s ^o _a ^c _r ^c ^{o d} _l ^{w l} _c ^e _{s n} ⁱ _t .ⁱ _c ⁱ _g M _d _T ^{e a} ^f _{i d i} tⁿⁱ _, _l ^h _t ^u _o ^{3 y} ^< _c ^s _{a s} ^a _n ^o _x ⁿ ^{o i} _s A _u ⁿ _s _i ^r _e ^a _l ^{c a} _e ^h _{s s} ^l _k ^e _e _e ^h _t ^t _{p i} ^s _t _s ^o ^c _d _E ^y _{a 1} ^± _t ^{n t} _a ^r ^{l e} _e ^d _{, st a} ^v _r w_n ^e _c ^e _{r a} ⁱ _o _d ^t ^R D _{8 o} _T ^cs _{r h} ^{t P} _. ^{t n} i ^{o t} _{n e} ^e _{t 3} ^e _h ^x ^t _e ^g _o ^{r r} _{a r} ^oi E ^d _{) r} ^e i ^e ^t _s ⁱ _s ^{n m} _s ⁿ _{i a} _{o ,} ^, ^d ₎ ^s _p ^ct _r ^p ₀ C ^y _{a 1} ^{+ y s} _f l_{t y} ^a _{v o} ^s _e ^e _l ^{c t} _{r e} ^s ₍ ^g _d ⁿ _n ^{a s} ^{n a} _{d s y d} ^{e 1} ^y _p ^{u c} _f ^s _s ^a _y ^oi _{si u} ^r _o ^y _c ⁱ _t f ^{a a} ₁ N D _{4 e a -} ^{o C} _{r d e} ^. _{i d e} A ⁿ ₇ w^{l r} _. ^{p m} _y ^b s_t ⁿ ₀ ^p N _a E _{. ±} ^d ^{( 7 ol} _{a o} m_. ^{r 1} _s ^y _s ⁱ _t ^d _{u t} ^{n n} _{e g} ^{i 6} _e ^r _t _T ^y _{a 2} ^m _r ^e ^e _{s t 3 l} ^o p ^o _d ⁿ _{e n f} ^w _a ^{r u} t _o ^y _{a a} ^{d i} _s ^t _{s e} ^m _s yⁿ _i ⁿ ^a _d ^{, s} _n ^D _i ^{v f m} _{t s} ^{s .} _{s l} ^{l h}t_{i e} N_I D _si ^t _s ^m _h A ^a _t ^t _y ^t _e ^h _{ti d} ^{e o} _{p r} ³ l ^a _r ^f _a ^{o o a} _o ^a _e ^s _t ⁿ _a ^{c w}m^s w_u ^S f t _f ^I _n ^o _e ^r _{t s} ^a _{e i} ⁿ _{s s} ^e M ^y _y _{a 1} ^p _a ^{r e} _e _h ^r t ^e _t ^S _l ⁿ _it ^{y s} _y ¹ _. i_t ^e _t m^e _il ^t _{n s} ^s ^{t a} _e ^e _i ^{t n} _b ^a _d ^t _n ⁾ _s ^a _r ^t _u ⁿ _{e r} ^{u c e} _{i a} D _e ^h _{t r} ^y ^e _d ^r _h t ^u _{t g} _s ^t _n _r ^u _o ^c _n ^e ^e _{s i} ^y i ^o _i ^t ₃ ^± _t ^a _a ^d _si ⁿi_t m _s ^h _{ti t} ^a _si _i ⁿ _i ^{n t} _a ^a _e ^w _p ^h _t _g ^y _f ^{a s} ^{n o} i_{t d} ^u _{f i} ^et_{f u} n _{8 t} ^{s o} _n ^{o a n d} _a i_t ^s _a ⁿ _{i s} ⁱ _p ^l ,_e ^h _o ^h m _o d^{c e}r m _s _a ^t _{n t}- _n ^t _ll _n ^a _e _r ^v _a _e ^{2 s} _y e - ^{1 e a} _d ^e _{s it s} ⁿ r_{- h} ^t ₀ ^{o a y} d_u ⁿ _{a o} ^wm ^c _{t r} ^d ^e _{e t} ^t t ⁱf _g ⁿ _n ^ei _e ^e ^h i _n _t ^{o g} _i ^e _i ^o r ^s f ^h l ^t _a ^{d d} _l c^y S_{a r} ³ i ^{d d n} _e D ^et_{f >} t_{s t} ^y _i ^c _i ^s _t ^a _t _e ^a _l ^{n )} _e ^a _p ^o f ^at ^P _e ^u o_{0 l} 1^u _o m^t _{d e} _a ^u _t ^p _o s ^d _p ^{, r} _e _{s o} ^{f h} _t ^e _i _l ^{b v .} t_g ^{n m} i_{r o} o^h f _s a ^{s d} _e ^cs ^{± h} _s ^er ^s _r ^e _s ^ht _i ^y _{a e} ^{b d} _{l a} ^{t n} _e ⁿ _{e r} ^y _t _{y a} ^h ^a t _i ^d ( U_t _g ^o _i _, w ^wd _i ^{d u} _p ^{e u} _q ^e _r ^e _p ⁱ _c ⁱ d ^m ^s _i ^m _f ⁰ ^o ₉ ^{F u} _r ^h _t ^r _{e s} ^l _{o e o} ^h _c ^{c er c} _{s e} ^b _x ^o ^t ₀ _a ^{3 n} _o n _o ^{r e} _y ^r _T L^{d a} ⁱ _{f t} ^a _e ^. _e ^h _t ⁿ _r ^{e h} _l ^m _r _y ^y _d ^{d o o} _s t _c ^a f_{r d a f} e _{si e} ^r _g ⁿ _i ^ll _t r _i ^c _a ⁱ ^d _g ⁿ _i s h _i ^s _{y d} ^v E ^l _e ^ut _, ⁿ _o ⁿ _{o n} ^o t ^c _e ^a _{d e} ^h : _i ^e _{p n} ⁱ _{a n o u} ^w _d _s ^t _{o s e} ⁿ _f ^{c t} _{a e} ^{t o} _i ^{t m} e ^d A^r _a _o ⁱ _i _r ^{e c}s _r ^z ^o s^e _i w^d ^f _{i 0 t} ^t ³ _fi ⁱ _s ⁱ m_n e^e m h ⁱ _g ⁱ _, ^y _t ^{n b} _b ^o _a ^{v d} _e G ^ct w^e _{f ,} ^{. d} _l ^{o n} _{i a} ^{h m} U_n _P ^{/ y} _t _{e a i} ⁿ _s ^o ^r D _{o d} ^l _r _a ^u _c ^g _{u :} ^ti _{n v r} _s ^o _{i p d} ^we r ^{o a} ^{e 1 c} _{s g} ^{. u} s_l m ^l _r ^Ma _c i _{d e o} ^{a a} _{x li} ^o _{f r} ⁱ _f _u d _y ^{- v c} ^m _e ^r _i ^v _o ^r _d ⁱ _t _{d y v} ^a _u ^u _{- t . t} ⁿ _{i o} ^{n ( h} _s ^s i ^e w ^r _e ^o _i w^a _u ^{1 s} ^v _a ^{w e} _r ^{o s t l} s_t ^p Oⁿ _g _e ^d ^c _u ^e _{r p r} ^{u l} _u ^d _p o _u ^{t u} - ⁿi_t ^{o l} ⁿ _{ll a} ^l ^{v T} _p ^t ^o i _r _s ^{i a} _t ^a _{n n} e _g ^{i o} _i ^e _a _s ^ci_s ⁱ _si ^e _b ^{H i} s C ^y o ^t ^r _S ^u _{s 1} _{e S} ^/ _{n h} ^s _s e w^o _o ^o l ^{c f} _{e S} ^I _e s ^, _t _P ^s _e ^{l i} _C ⁿ _i ^t _{v r} ^t e ^e _s ^t _a ^{n y v} _d r _{c h} ^{e n} _{i o} ^c _h ^c _i ^l _u ^E _l ^l ^d _a ^c P ^{y o} _i ^t ^{s i} _{s u} iⁿ _l i_t ^o _i f ^{d m} _r ^e _si ^{v E} R_n ^l ^a _b ^t ^a _v _{t s} ⁿ _I ^m _a ^{d p} e ^{d n} e_i ^{l o} _r _{c h} ^{s a} _i _d ⁿi d_{C s v} ⁿ ^o _e ^e _{r T o} ^y ^c _{t f} e^o ._s t-_f ^{e u} _t ^g _n ^U _y _F ^{b w} _e ^{p e} _{v e} ^x o ⁿ _e ^{c e}i ^h _{t e} ^m _r ^t ^o _e ^g _{e s} ⁿ _l ^c r m G _a ^{t h} ^l m ^g _o ^O _{s t} r _E ⁱ _d ^a _S ^a _d ^at _s ^o L ^T L ^D _P ^f _{c l} _o A^e _b ^y _d _b ⁿ _f _a ⁿ _I ^a T ^o _S ^C s t_i _E A w B ^o _{h P a b c d e f g h} O s_t ⁿ _d ⁸ _s ^{t y l} _i ^W _e ^a _h ^y _{a n} ^t _t ^a ^e _a D _n ₁ m _e ^{u d} ⁰ _/ ^s _s ^v _a D_i ^t n_a ^p _e ^v _{r e} ^t ^{3 e} _a ^e _{t c} f^el _{0 s} ^h ^s ⁰ _a ^{o o r} h₎ ^s _o ^h _{a l} ^o _{- y} ^{t F o} t ^e _{r c} O ^{g w} _s _o ^r _o ^{e .} t_d ^{e e e} _{h e} _r ^b ⁱ _u ^{n t} ) ^llK ^l _o ^{t ,} N _{a t n} n^o _{u i} ^t _n ^s _i _{e i} ^{t q} _e ^o _y ^{a w} ^{O m} _e _: ^{h m} _c _t ^{n r} ^e _r ^a _u ^f _{s c d} a _d ^l ₄ ^b _a _u ^{1 m} _u _c ^o _e ⁿ _f ^r _{t r} _e ^{s f e} _e _v ^{l o ± zi} ⁱ _c ^y _h ^{s (} ^s _l ^o ^r _e _e ^l _o ^f _p t ^l _{c s} _r ^t _{k z} ^e ^{a d} _{n h} ^c _n ^{e e} _{e t} _e m^{a t} _s ^a _a ^e _i ^{t w} _. ^A ^R s ^{y e} _{e ,} ^y _{f a} ^{2 r} _e ^f _o _h ^h _{t r} _e ^T _e ^{t o p} s_i ¹ _{e .} s^y _{t 1} ^t i^l _{y a} ^l _n ^o ⁿ _r ^{. c} g_n ^y _e i m^e _a ^{h t} _a ^r m _{e s} v^r i u_t ^a _r ^{o n} t _i s _h ^{D, r} _e ^c _t ^s _o ^{y c n} _{3 c} ^t _s _{o e o n} ^o _i ⁿ A ^d _ti ^{l m} ^e _{a u st} ^l _c ⁿ _b ^e ^a _h ^{t r} _{e i} .^ti _s _r ^{r n y y} _, ^v ^o m^r _e ^s _{e C r} ^{o 4} _e m^{d i} ^h _{a v} _f ^e _o ^, m b ⁿ _{b y} ^s _d _s ⁿ _{t 5 c} _o ^a _{r k} ⁱ _{e T} _h ^h _t O d ^{a g} _o ^e _s ^{y o e} _e ^w _g ^E ^e _s ^{y l} ^s _{r o} ^s _{a e} ^b _b ^{a , n} _{i e} _e ^o ^s _t ^t _a ^y _l W_n _r ^e _{l e} ^l _i ^o _{i .} ^e _l w^h t^t s ^a ^a _r ^{mo c h t} _t ^{c o}l _a o _{e t y t n} ^a _{u y l} ,_r d _b ^{h a} n ^a _{( r} ^{c f u} ^{o y} _{o ,} ⁿi_t ^{c o} ^y f ^e ^a _l ^{. d} t_f _e ¹ _st ⁿ _b ^a _{n n} ¹ ^l _l ^{a o}i ^{y n} _{o a} ^d _{- e} ^l _e ^a _e _b ^e _e a _d ^l _{a f} ^o _t ^u _a _l ^c l ^D _si ¹ _c m^r 2 ^{y r} _e ^h ^{i a} _r ^m _s _a ^{s c} _i ^{n 1 o} _{s s} ^{1 d} _{c o} _{t h y} ^f _t _s ^s ^{v G} _e _a _e ^{> s} _{s il} ^y _a ^e _r ^g _n ^e _l ⁿ _e ^c _a ^a _d ^e _{i e} ^l _c b^{a a c} e ^D _{t e} ⁱ ^h _d ^{c e - d} ⁿ _y ^m _t ^f ₁ ² _o ^y _{c 1} _t ^{d y} _r ^v _a ^a _t s _{e t} l c^o _{t i} i_f ^{C a} _{e o} ₄ ^{y b} _{it 6} ¹ ^{a h} ^{o n} _e ^t _n ^. _k ^r ^c m ^{tr 1} _r ^{e n} _{a y} ^r ₁ _u m _n ^e _r ^o _t _{g i} ^r _{e b} ^e m^{t u} _g ^{ni i} _t ^o ^s _r ^f _o ^y _{a v} ^e _{g e} ^v ^a _{u a} ^y ^e t_i ^l _s ^o _p ⁱ ₎ ^s _T D _f ^{o u} _{r e} n_i ^{s p} o_x ^l ^{e l n} _i _a ^t _r ^t _{a d d y} ^S ^c _{n f} ^a _{I h} ^{g 1 d}-_{i d} ⁿ i ^{o o m} _{r o} ^t _e ⁿ _{i d} ^C E_u ^{o y} _a ^t _{n a} d ⁾ _t _s ^{o n} ⁽ _n i _{c t} ^{r o} _{n r} ^o _r ^u ₇ ^{R i} _r ⁶ ^{h D e a} _{f 2} ¹ g^u _{e l} ^c _d ^l _{u a} ^{t b} _a i_r ^{t ±} ( ^r t ⁿ _l ^{b o} _t ^e _l _r ^{v e o} _s e _e ^p ^d _a ^h _h ^t _h ^s _h ^{t h} _{t s n} r^a h_c ^s ⁱ _{k e} ^{p 1} ^y _{o a} f ^e _n ^{t n c} _y _{e ,} ^e _a ^oi _{) e} m^C ^y _d ^o _, ^e _s ^t _r ^{e o} _{t 2 i} ⁿ w_l ^b ^u _h i ^D _s ^m ^u _{u s} ^s _, ⁹ t ^{s w} _d ^a _n ^e _i ^t _f ^{t 7} _g ⁱ _{9 s} ^{s n} _{o f} ^r _{e e} ^{s e} _l _{f s r} ^{g t} _a ^a ^s _n ^{a n} _{i s} y _{y o} s_t ⁿ i ^s _{, s} ^{a c} ^{o t} _n ^{y p} _e ⁱ _v ^{e h}t_{i l} ^{l r} _e ^{pf e} _l ^s _u ^{s e} _y C ^{y e} _i ^t _i ^{l e} _s t_i ^l _l ^e w _a ^{c v} _e ^{i, b} _a ^o _{C h} ^t _, _a ^t _a ^e _{a r i d} ^t _n ^M _r ⁶ ^d _{a h s n} ⁿ _{i n} ⁿ _l ^e _{v B} ^e ^e _h ^{. p} ^r m^{r T}m^r _t ^{n w} ^t _g ⁿ _{o o} ^{n .} _a ^l _c ^e _{h a} ^a _r ^{a P o} f _l _{d o} ^c ⁿ _e ^r _{d p} ^t _r _{, 1} ^{. o} _{t ,} ^{d s} _{e y} _r ⁱ ^o _s ^F f ^o _{: b} _{d d} ^{8 a e} _{ri b} ^m ^a _s ^s _e ^{u g} ₁ ^a _i ⁿ _{i o} ^{o l} _p ^C _, y^{u y} _e e^{s b} w^o _n ⁱ _{n T} ^v ^S _y ^b _l ^b m ³ l_o ^{t y} _{a r} ^o _q ^e _{r s} ⁿ _a l_l ^e _I .₎ ^D _I ^{d e a} _s ^e _l u_{d r} D_{t r} ^o ^t _t ^{a a c o} _{f e} ^{r C 6 B} _e ^r _l ^{o c} _y e^o _i ^, _s ^a _{r o r} _{h r} ^e _l ^o _b ^{n o y} _r ^st b ^o _{t s} ^{e o} _c _t ^S _E ^e ^{t R} _l ^d _e _r ^b _e ^t _h ^m ^r _si ^w _u ^C ( ^r _{e ,} c_s ^p s ^{c a} _l ^e _r ^a _l ^a _{r t} ^y _{l a} ^e _a ^t _e ^{t n} _i ^{s S 2} s_t ^r ⁿ _{h y} ^c _e ^a ₃ ^{o l} _a ⁿ _s ^r _p ( s _si m _e ^l _: ^{s e} _l _{e 2} ^{t n} ⁷ _n ^e _i ^l _e ^{l >} _b _{e c} ^{a n} ^{y e ll} _{o o} i _{u n} t_{i d} ^{e c} _c ^oi _e _s ^l _p ⁿ _i ^d m _{a p e} _e m ^{l c} p_y C m^s _s ⁿ _{i u} ^s ^e _s ^ht ^q _{e a c d} b^{h a} _a _{c r} ^c _i ^d r .^. _{d i} ^{u o s} _e m ^d q_t ^{r a} _{s a} ^{b a} _s m^, ₁ _e ^{ll c} _i ^a _{s e} s _i ^s _f _a w _b ^a Gⁿ _i u^o _{e e} ^{c l} _{c x} ⁱ _x ^{i a} _r ^{o e n} _{e g} ^{o c} f _r s ^m _r _{y n s} ^{g f p} _i ^{t b} _i l^{l w m} _a ^{yt l} i_c ^y ^g _o w _{d n} ⁱ _{o n 5 d} ₅ ^e _i ^{1 n} _d l^a _e ⁿ _e ^s _{i s} _e ^s ^l _{y e} ^c _e ⁿ _i ^b ^s _{i i} ^{k w} _a ^{n c} _{i C} _{t y} ^{d n} _{e n} _{o r} ⁿ ^{t d} _{a n} _a ^e ₃ ^e _s ^{1 r} _e ^y e ^r _o ^y _a ^p _a ^{p p} _p ^p _{o s} ^h _{p o} ^{a m} _{u o} ^{g o} x ^e D _p A _p A m^{a c a a} _r ^c _a ^t _s ^zi ^c _{a o} ^e _s _{s s} ^{o r} _o ^g m ^o _{b l} ^{o m n} _u ^o ^m _b ^l _c ^wD^o _d ^{n e} _{e e r} ^c m_o ^{i r} _a ^a _{l z} ^e _r ^a m_d _{e n} ^y _{d h a} _a w _{8 e} ^{S e} _S ^h _{i d t e} H^a _{c C} ^o _n ⁿ _T M ^u T ^a _r ^h _P ^a T A _h ^{P m} _I ^r _p j _k m _{n o p r s u v} w _x Attorney Reference: ONKO-003/01WO ^y Study team will maintain regular daily contact with the patient during Day 1 through 8 of Cycle 1 to review self- collected BP measurements and to assess for any symptomatology ^Z In Cycle 1, patients will perform at home blood pressure monitoring at least twice daily during the treatment period, once in the morning and once in the late afternoon/evening. Patients must take their PB prior to dosing in the morning and the evening. Patient must not take their dose if their BP is below 100 mmHg systolic or 50 mmHg diastolic. Patient must report any values below this to the study physician immediately. The study physician will provide the patient further instruction if needed. Patient will keep a log of blood pressure values and bring the log with them to every clinic visit during Cycle 1 for review by the study team. Table 6: Pharmacokinetic and Pharmacodynamic Sample Collection Times

^ddose of talabostat and Atezolizumab infusion. Predose for cytokines is defined as a time period within 30 min before the planned morning dose of Talabostat Attorney Reference: ONKO-003/01WO Example 2 Phase II trial of Talabostat mesylate and Pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma Objectives: [0472] Primary Objectives: 1. To determine the progression-free survival (PFS) rate at 18 weeks on study (PFS18 weeks). [0473] Secondary Objectives [0474] 1. Safety and tolerability [0475] 2. Objective response rate (ORR) [0476] 3.Median duration of response (mDOR) [0477] 4. Median progression-free survival (mPFS) [0478] 5. Median overall survival (mOS) [0479] 6. Change in tumor marker (CA19-9) [0480] Exploratory Objectives: [0481] 1. Pharmacodynamics markers of fibrosis [0482] 2.Circulating KRAS mutated DNA [0483] ^^^7LVVXH^JUDQ]\PH^%^^Ȗ,)1^^,/-6, and CXCL9 ENDPOINTS [0484] Primary Endpoints [0485] Progression-free survival at 18 weeks (PFS18 weeks) [0486] Secondary Endpoints [0487] Adverse events as per CTCAE v.5.0 Attorney Reference: ONKO-003/01WO [0488] Objective response by iRECIST v.1.1 [0489] Duration of response (DOR) [0490] Progression-free survival (PFS) [0491] Overall survival (OS) [0492] Change in tumor marker (CA19-9) [0493] Study Intervention Talabostat mesylate [0494] Talabostat mesylate will be administered 0.2 mg by mouth twice daily days 1-7 during Cycle 1, and if deemed appropriate by the investigator after review of the patient’s labs, vital signs, and adverse events, dosing will be increased to 0.3 mg by mouth twice daily days 8-14 of Cycle 1 and in subsequent cycles will continue 0.3 mg mouth twice daily days 1-14 every 21 days. Patients should not be escalated to 0.3 mg by mouth twice daily if they experienced any grade 1 or greater adverse event considered related to Talabostat or skipped any doses due to hypotension or orthostasis during days 1-7. Pembrolizumab [0495] Pembrolizumab will be administered 200 mg IV over 30 minutes every 3 weeks for up to a maximum of 2 years. [0496] Pembrolizumab will be sourced by Merck through their Investigator Studies Program (MISP). The storage, handling, and preparation of Pembrolizumab will be performed in accordance with the FDA label: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s131lbl.pdf [0497] SAFETY LEAD-IN [0498] The first 6 patients enrolled will be followed for 6 weeks (safety window) as part of a safety lead-in. Enrollment will be stopped if there is evidence of excessive toxicity in the first 6 patients Attorney Reference: ONKO-003/01WO as defined below. In the event of enrollment being stopped, the protocol may be amended to enroll patients at a different baseline dose level. Enrollment will be temporarily held following the enrollment of the sixth patient until they complete the safety window, and safety data will be reviewed by the Data Safety Monitoring Committee at that time.Enrollment will resume following approval by the Data Safety Monitoring Committee. [0499] Evidence of Excessive Toxicity for Talabostat mesylate (as Attributed by the Investigator): Any death not due to underlying disease or extraneous causes Grade 4 hypotension Grade 3 fatigue lasting more than 7 days Grade 4 thrombocytopenia Grade 4 white blood cell count decreased G^{rade 4 acute kidney injury} [0500] Dose Modifications for Talabostat mesylate: ^{[0501] Dose levels for Talabostat mesylate are:} ^{1: 0.3 mg by mouth twice daily days 1-14 every 21 days} -_{1: 0.2 mg by mouth twice daily days 1-14 every 21 days} _{-2: 0.1 mg by mouth twice daily days 1-14 every 21 days} _{-3: discontinue Talabostat mesylate} [0502] No further dose modifications will be permitted beyond level -2, and dose re-escalation will not be allowed. [0503] Talabostat mesylate tablets contain valine-proline boronic acid formulated as the methanesulfonate salt. Current dosage strengths include 0.05-mg, 0.1-mg and 0.2-mg tablets for oral administration. Additional dosing schedules may also be evaluated during the Lead-In Stage. [0504] To minimize risk of hypotension, patients should be advised to maintain adequate hydration while on-treatment, such as drinking at least 2 litres of fluids per day, including fluids with electrolytes. Factors such as strenuous exercise, heat, humidity, fever, gastrointestinal disturbance may increase hydration needs. Administration of at least 1L of IV fluids is required at Attorney Reference: ONKO-003/01WO Cycle 1 Day 1. It is at the investigator’s discretion to provide IV hydration during in-person clinic visits beyond Cycle 1 Day 1. The patient may be monitored overnight at the discretion of the Investigator. If the overnight monitoring is not associated with any Grade 2 or greater AE or any other SAE criteria, the admission will not be considered an SAE. Longer periods of in-patient monitoring may be implemented at the discretion of the Investigator. [0505] Talabostat mesylate will be administered orally as 0.05-mg, 0.1-mg and 0.2-mg tablets. Patients will take the prescribed number of tablets on Days 1 to 14 of each cycle, for a total daily dose of 0.4 mg, 0.6 mg, or an intermediate dose. Talabostat mesylate will be continued until PD or unacceptable toxicity. Talabostat mesylate should not be taken on an empty stomach. [0506] On days when pharmacodynamic studies are being performed, Talabostat mesylate should be administered at the study center, and should be administered at (approximately) the same times of day on each treatment day in the cycle. In cycles in which pharmacodynamics are not evaluated, Talabostat mesylate also should be administered at (approximately) the same times of day on each treatment day in the cycle. [0507] During days 1-14 of cycle 1, the patient will perform at home blood pressure monitoring at least twice daily, once in the morning and once in the late afternoon/evening. The patient will be provided with a log to record blood pressure measurements and will be asked to bring the log with them to every clinic visit during cycle 1. The patient will be reminded of oral hydration guidelines, review side effects, and review the patient’s self-administered blood pressure measurements. The patient will be instructed to hold Talabostat mesylate for any blood pressure with systolic below 100 mmHg or diastolic below 50 mmHg and report these values immediately to study personnel. The investigator will provide the patient further instruction if needed. [0508] Doses should be taken at approximately the same time every day. Doses held because of AEs should not be made up on subsequent days within or following a cycle. A dose that is missed for reasons other than an AE (e.g., the patient forgets to take a dose) may be taken at least 6 hours prior to the next planned dose; otherwise, the missed dose may be administered on a day subsequent to the scheduled dose. Any additional adjustments should be discussed with the medical monitor or designee. If a dose is vomited within approximately 10 minutes of dosing, the patient may be re-dosed. If the patient vomits >10 minutes after dosing, no further attempts at Attorney Reference: ONKO-003/01WO dosing that particular dose should take place; dosing should resume with the next dose. Under no circumstances should missed doses be made-up when the patient is already taking a planned dose (i.e., no “doubling-up” to account for missed doses). [0509] If an SAE thought to be related to Talabostat mesylate occurs during the treatment period, dosing of Talabostat mesylate should be interrupted in that patient until the SAE resolves. If the investigator wishes to continue the patient on Talabostat mesylate, the medical monitor should be contacted to discuss continuing Talabostat mesylate at the same or reduced dose. [0510] The most frequently observed AEs that appear to be characteristic of Talabostat mesylate are edema/peripheral swelling, hypotension, dizziness, and hypovolemia. These events, including edema, tend to be manageable and reversible and usually resolve following a drug hold. Talabostat mesylate should be held for Grade 2 or higher episodes of such events, until resolution of these AEs. Talabostat mesylate can be restarted at full dose after resolution of these AEs, including edema. For other Grade 2 or higher AEs deemed related to Talabostat mesylate, or for edema that has not responded to drug hold, the dose of Talabostat mesylate can be reduced by 0.2 mg decrements of the total daily dose at the discretion of the investigator. [0511] Discontinuation of Talabostat mesylate should occur for any life-threatening AE, or for Grade 2 or higher treatment-related AEs that do not respond to dose reduction to a 0.2 mg total daily dose. [0512] If Talabostat mesylate is discontinued then the Pembrolizumab would also be discontinued and the patient would go off treatment. ^{[0513] Pembrolizumab} T_{he planned dose of Pembrolizumab for this study is 200 mg every 3 weeks (Q3W). .} [0514] Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Attorney Reference: ONKO-003/01WO [0515] The Pharmacy Manual contains specific instructions for the preparation of the Pembrolizumab infusion fluid and administration of infusion solution. [0516] In the event that Pembrolizumab is discontinued, the patient may continue on Talabostat mesylate at the discretion of the Investigator but if Talabostat mesylate is discontinued then the Pembrolizumab would also be discontinued and the patient would go off treatment. Prohibited Medications [0517] The following medications and vaccinations are prohibited during the study: Live or attenuated vaccines within 30 days before the first dose of study intervention and while participating in the study. [0518] Note: Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed in the study as long as they are mRNA vaccines, replication-incompetent adenoviral vaccines, or inactivated vaccines. These vaccines will be treated just as any other concomitant therapy. Systemic glucocorticoids except when used for the following purposes: To modulate symptoms of an AE that is suspected to have an immunologic etiology For the prevention of emesis To premedicate for IV contrast allergies To treat asthma or COPD exacerbations (only short-term oral or IV use in doses >10 mg/day prednisone equivalent) For chronic systemic replacement not to exceed 10 mg/day prednisone equivalent [0519] Other glucocorticoid use except when used for the following purposes: For topical use or ocular use Intraarticular joint use For inhalation in the management of asthma or chronic obstructive pulmonary disease [0520] If there is a clinical indication for any medications or vaccinations prohibited, the investigator must discuss any questions regarding this with the Sponsor. The final decision on any supportive therapy or vaccination rests with the investigator and/or the participant's primary Attorney Reference: ONKO-003/01WO physician. However, the decision to continue the participant on study intervention requires the mutual agreement of the investigator and the Sponsor. [0521] If the investigator determines that a participant requires any of the following prohibited medications and vaccinations for any reason during the study intervention period, study intervention must be discontinued: Systemic antineoplastic chemotherapy, immunotherapy or biological therapy not specified in this protocol Investigational agents other than those specified in the protocol Radiation therapy [0522] Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be allowed at the investigator’s discretion. x Investigational vaccines (ie. those not licensed or approved for Emergency Use) are not allowed [0523] All treatments that the investigator considers necessary for a participant’s welfare may be administered at the discretion of the investigator in keeping with the community standards of medical care. All concomitant medication will be recorded on the case report form (CRF) including all prescription, over-the-counter (OTC), herbal supplements, and IV medications and fluids. If changes occur during the trial period, documentation of drug dosage, frequency, route, and date may also be included on the CRF. [0524] All concomitant medications received within 28 days prior to the first dose of trial intervention and up to 30 days after the last dose of trial intervention should be recorded. If participants experience an SAE or Events of Clinical Interest (ECI), concomitant medications administered 30 days after the last dose of trial intervention are to be recorded as defined in iRECIST. [0525] Participants should receive appropriate supportive care measures as deemed necessary by the treating investigator. [0526] Procedures Involved (refer to Table 7) Attorney Reference: ONKO-003/01WO 1. Long term follow up will occur via clinic visit or phone call every 3 months following end of treatment for up to 24 months. 2. iRECIST Imaging should consist of CT/MRI of chest, abdomen, and pelvis. Study tumor measurements will be assessed using iRECIST (Seymour et al. Lancet Oncol, 2017). Treatment beyond progression is allowed if the investigator and patient believe continuing study therapy is in the patient’s best interest in the absence of new lesions until a confirmatory follow-up scan demonstrates clear evidence of disease progression per iRECIST. [0527] Tissue and Blood Specimen Handling 1.1 Patients will undergo a pre-treatment core tumor biopsy during the screening period and on-treatment biopsy (C2D15 ± 7 days). When possible, the same lesion should be biopsied on both occasions. Bone lesions are not to be used for the serial biopsy unless there is a soft tissue component amenable to biopsy. At least 31-2 cm core biopsies will be obtained using an 18-20 gauge needle per standard interventional radiology protocols. Specimens will be labelled with the patients 3-digit trial number and the number “1” to signify the pre-treatment biopsy or the number “2” to signify the on-treatment biopsy. Tissue samples will be immediately placed in formalin and then embedded in paraffin (FFPE). Specimens will be sent to Dr. Weiner’s lab at 3970 Reservoir Road NW, Washington, DC 200057. 1.2 Imaging Mass Cytometry (IMC) Panel to Analyze the PDAC TME The IMC panel will use the Fluidigm platform to concurrently analyze biomarkers following work by Peran and colleagues (Peran et al. Gastroenterology, 2021). 1.3 Research blood samples will be collected on D1 of each treatment cycle (every 3 weeks) and at the time of the on-treatment biopsy (C2D15 ± 7 days). Circulating tumor DNA (ctDNA) for KRAS (Sacher et al. JAMA Oncol, 2016) will be collected by filling a 10 mL purple top (EDTA) tube, inverted 8-10 times, and stored at Attorney Reference: ONKO-003/01WO room temperature until centrifugation which will be within 4 hours of blood collection. Plasma will then be separated and stored at -80C. DNA will be extracted using Qiagen’s QIamp circulating nucleic acid kit and quantified using the Nanodrop PicoGreen assy. Genotyping will be performed using droplet digital polymerase chain reaction (ddPCR) and data analyzed using a Bio-Rad machine. PBMC will be isolated by Ficoll density gradient centrifugation from the blood cells and stored at -^^^&^IRU^IXWXUH^LQWHUURJation. Circulating fibrosis markers associated with PDAC will be assessed by filling 2 x 10 mL red top tubes and analyzed using ELISAs as outlined by Resovi and colleagues (Resovi et al. EMBO Mol Med, 2018). These markers include MMP12, MMP13, IGFBP4, IGFBP5, SPARC, ES, PDGF-BB, FGF-2, VEGFA, TIMP1, sICAM1, MMP7, PICP, PLG, TSP2, IGFBP2, FN, PINP, CCN1, CCN2, sVCAM1, NGAL, Col4, and Lam-P1. IL-6 will be measured in the blood by ELISA using commercially available kits. [0528] Data Obtained from Specimens Research data will be gathered from study specimens and recorded using 3-digit study identifiers for individual patients. All data will be stored in an online, encrypted database accessible only by study personnel. Patients consent that information related to study specimens may not be revealed to patients and that specimens will not be returned to patients. [0529] Sharing of Results with Subjects Investigators may reveal study results with subjects once such information becomes publicly available and/or it is added to the informed consent form. [0530] Study Timelines Patients will remain on study treatment as long as they have not had disease progression by iRECIST, they wish to remain on the study, and the treating investigator agrees that it is in the patient’s best interest to remain on the study (e.g. patient is tolerating study therapy and deriving clinical benefit). Patients will continue long term follow up following completion of study treatment for 2 years. We anticipate enrolling all subjects within 36 months of study opening, with the ability to assess the primary endpoint within 40.5 months Attorney Reference: ONKO-003/01WO of study opening, estimating study completion within 42 months of study opening and publication of primary endpoint results within 50 months of study opening. [0531] Inclusion and Exclusion Criteria [0532] Inclusion criteria: 1. Histologically-confirmed pancreatic ductal adenocarcinoma with metastatic disease (mixed histology is acceptable as long as adenocarcinoma is the dominant histological subtype) 2. Patient must consent to two mandatory biopsies and have tumor amenable to serial core biopsies 3. MeasurabOH^GLVHDVH^E\^L5(&,67^Y^^^^^^FULWHULD^^WXPRU^^^^^FP^LQ^ORQJHVW^GLDPHWHU^RQ^ D[LDO^LPDJH^RQ^&7^RU^05,^DQG^RU^O\PSK^QRGH^V^^^^^^^^FP^LQ^VKRUW^D[LV^RQ^&7^RU^05,^^ on baseline imaging 4. Documented progression of disease or intolerance on at least one regimen for metastatic disease (progression during or within 3 months of the completion of neoadjuvant/adjuvant therapy is acceptable) 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 6. $JH^^^^^^\HDUV 7. Criteria for known Hepatitis B and C positive subjects a. Hepatitis B and C screening tests are not required unless: i. Known history of HBV or HCV infection ii. As mandated by local health authority

Attorney Reference: ONKO-003/01WO iii. Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. iv. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post-completion of study intervention. v. Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening; participants must have completed curative anti-viral therapy at least 4 weeks prior to C1D1. Subjects with no brain metastases or a history of previously treated brain metastases who have been treated by surgery or stereotactic radiosurgery (SRS) at least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of active intracranial disease Patients with available standard 12-lead ECG with the following parameters at screening (defined as the mean of the triplicate ECGs): a. QTcB (Bazett’s formula) interval at screening <480msec %RQH^PDUURZ^IXQFWLRQ^^DEVROXWH^QHXWURSKLO^FRXQW^^$1&^^^^^^^^^^PP³^^3ODWHOHWV^^^^^^î^^^^9/L; KHPRJORELQ^^^^^^^J^G/^^ZLWK^QR^SUior red blood cell transfusions during the prior 14 days) 5HQDO^IXQFWLRQ^^VHUXP^FUHDWLQLQH^^^^^^^î^XSSHU^QRUPDO^OLPLW^RI^LQVWLWXWLRQ^V^QRUPDO^UDQJH^RU^ FUHDWLQLQH^FOHDUDQFH^^^^^^P/^PLQ^^^^^^P² for subjects with creatinine levels above institutional normal +HSDWLF^IXQFWLRQ^^$67^DQG^$/7^^^^^^^î^WKH^XSSHU^QRUPDO^OLPLt of institution's normal range. 7RWDO^ELOLUXELQ^^^^^^^î^WKH^XSSHU^QRUPDO^OLPLW^RI^LQVWLWXWLRQ^V^QRUPDO^UDQJH^^)RU^VXEMHFWV^ZLWK^ liver metastases, AST and ALT < 5 × the upper normal limit of institution's normal range, and total bilirubin >1.5 - 3.0 x the upper normal limit of institution's normal range are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia. Attorney Reference: ONKO-003/01WO 13. International normalized ratio (INR) or prothrombin time (PT) d 1.5 x the upper limit of normal unless patient is receiving anticoagulant therapy as long as the PT or aPTT is within the therapeutic range of intended use of anticoagulants 14. Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring “Twilight” sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with the Principal Investigator. 15. Women of childbearing potential must have a negative serum pregnancy test during the screening period and on C1D1 and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential 16. Patient is capable of swallowing pills whole. 17. Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. 18. 3DWLHQW¶V^DFXWH^WR[LF^HIIHFWV^RI^SUHYLRXV^DQWLFDQFHU^WKHUDS\^KDYH^UHVROYHG^WR^^^*UDGH^^^H[FHSW^ for Grade 2 peripheral neuropathy or any grade of alopecia. 19. Male patients and their female partners of childbearing potential who engage in vaginal sex must agree and commit to use a barrier contraception (e.g., condom with spermicidal foam/gel/film/cream/ suppository) throughout the duration of the study until at least 6 months following the last dose of study drug, in addition to their female partners using either an intrauterine device or hormonal contraception and continuing until at least 6 months following the last dose of study drug. This criterion may be waived for male patients who have had a vasectomy >6 months before signing the informed consent form. [0533] Exclusion criteria: 1. Prior anti-tumor therapy within 4 weeks of C1D1 (defined as, but not limited to, anti-cancer agents (cytotoxic chemotherapy, immunotherapy, biologic therapy, and Attorney Reference: ONKO-003/01WO investigational agents), and radiotherapy within 2 weeks of C1D1, the “washout period.” Patients previously exposed to FAP inhibitors, DPP inhibitors, or monoclonal antibodies targeting anti-PD-1, anti-PD-L1, anti-PD-L2, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137). Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic symptomatic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial, or viral infection). Patient has a history of allogenic tissue/solid organ transplant. Women who are pregnant or breastfeeding; women of child bearing potential whose pregnancy test is positive within 72 hours prior to enrollment. Psychiatric illness or social situation that would limit compliance with study requirements. Concurrent malignancy or malignancy within 2 years prior to C1D1, with the exception of adequately treated cutaneous basal or squamous cell carcinoma, non- melanomatous skin cancer, curatively resected cervical cancer, or any locally treated malignancy deemed low likelihood for recurrence or metastasis by the investigator. Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria: At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment Clinically stable CNS tumor at the time of screening and not receiving steroids at least 14 days prior to C1D1 and/or enzyme-inducing anti-epileptic medications for brain metastases. Attorney Reference: ONKO-003/01WO Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patient has a known history of HIV infection or chronic, active hepatitis B or C (testing is not mandatory) – patients with hepatitis B and/or hepatitis C status-post treatment with undetectable viral load are eligible (see above inclusion criteria) Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.). Patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the investigator would put the patient at significant risk for pulmonary complications during the study. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following: History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening History of documented congestive heart failure (New York Heart Association functional classification III-IV) Documented cardiomyopathy Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block) Attorney Reference: ONKO-003/01WO Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication Inability to determine the QT interval on screening Patients with history of symptomatic orthostatic hypotension within 3 months prior to enrollment^^GHILQHG^DV^D^GURS^LQ^V\VWROLF^EORRG^SUHVVXUH^^6%3^^RI^^^^^^PP+J^RU^ GLDVWROLF^ EORRG^ SUHVVXUH^ ^'%3^^ RI^ ^^ ^^^ PP+J^ZLWK^ DVVXPSWLRQ^ RI^ DQ^ XSULJKW^ posture. Patients with a history of (non-infectious) pneumonitis that required steroids, current pneumonitis, or those who have a history of interstitial lung disease. Patients who have received a live-virus vaccination within 30 days of planned treatment start date, killed vaccines are allowed. Patient must not have active known or suspected autoimmune disease requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (e.g., celiac disease) are permitted to enroll. Patient must not have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses Attorney Reference: ONKO-003/01WO ^^^^ PJ^ GDLO\^ SUHGQLVRQH^ HTXLYDOHQWV^ DUH^ SHUPLWWHG^ LQ^ WKH^ DEVHQFH^ RI^ DFWLYH^ autoimmune disease. 30. Prisoners. [0534] Statistical Considerations [0535] Statistical analysis plan [0536] Descriptive statistics will be used to characterize the immune biomarkers during the combination treatment as well as several long-term time points. Frequency and percentages for categorical variables, and mean (standard deviation) or median (IQR interquartile range) for the continuous variables based on the normalization of the data. Univariate test will be performed in terms of identifying the association between immune biomarkers or biomarkers and success or failure of response to the combination therapy, Chi-square test/Fisher’s exact test for categorical variables, and t-test/ANOVA or their non-parametric version for the continuous variables based on the normalization of the data. For survival endpoints (PFS and OS), Kaplan–Meier curves will be used to describe the survival distributions. Exact confidence intervals of the response rate and PFS18 weeks will be calculated. Kaplan-Meier analysis will be used to describe patient survival. The statistical analysis of the correlative data will be exploratory analysis. Since the estimated accrual is 1.2 per month, the study is expected to complete within 36 months. P-value less than 0.05 will be considered significant. All statistical analyses will be performed using RStudio (Version 0.99.902) and SAS (Version 9.4). [0537] Adverse Event Severity [0538] The study investigator will rate the severity of each adverse event according to the NCI CTCAE Version 5.0. For adverse events not captured by the NCI CTCAE Version 5.0, the following should be used: 1) Grade 1 (Mild) The adverse event is transient and easily tolerated by the subject. 2) Grade 2 (Moderate) The adverse event causes the subject discomfort and interrupts the subject's usual activities. Attorney Reference: ONKO-003/01WO 3) Grade 3/4 (Severe or Life Threatening) The adverse event causes considerable interference with the subject's usual activities and may be incapacitating or life- threatening. 4) Grade 5 (Death) The adverse event resulted in death of the subject. Table 7: Study Activities F ll w Up 24 s) In In _C _D _M E C _C A _A _V H W H _e B _M B _R T C E A E Ǻ

Attorney Reference: ONKO-003/01WO Follow Up 24 s) C C _L P T U C R P T A _F S

^aEastem Cooperative Oncology Group Performance Status ^bDaily during the dosing period of Cycle 1, the patient will perform home BP monitoring BIP prior to dosing talabostat and log the values. ^cDuring C1D1-14, there will be regular daily contact with the patient to review oral hydration guidelines, review the side effects, and BP log. ^dTumor biopsy will occur on C2D15 ± 7 days ^eCT/MRI will occur during screening and every 9 weeks on study ± 7 days ^fECG will be performed I triplicate prior to collection of blood samples; QTcB will only be measured at screening. ^gSeruP^ȕ-hCG will be measured at screening, C1D1, and every 9 weeks on study when appropriate (women of childbearing potential) Attorney Reference: ONKO-003/01WO ^hEither talabostat or pembrolizumab may be administered first, however, on C1D1 pembrolizumab should be administered first. ⁱIL of IV NS id required prior to talabostat on C1D1 and is optional whether to continue to administer IVF during D1 or more of subsequent cycles.

Claims

Attorney Reference: ONKO-003/01WO CLAIMS What is claimed is: 1. A treatment regimen for treating small cell lung cancer (SCLC) in a subject, the treatment regimen comprising administering to the subject an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist, wherein the talabostat or the pharmaceutically acceptable salt thereof and the PD-1 axis antagonist are administered in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 2. A method of treating small cell lung cancer (SCLC) in a subject, the method comprising administering to the subject an effective amount of talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the PD-1 axis antagonist are administered to the subject in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 3. A treatment regimen for treating small cell lung cancer (SCLC) in a subject, the treatment regimen comprising administering to the subject an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-L1 antagonist, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the PD-L1 antagonist are administered in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 4. A method of treating small cell lung cancer (SCLC) in a subject, the method comprising administering to the subject an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-L1 antagonist, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the PD-L1 antagonist are administered to the subject in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration 5. The treatment regimen according to claim 1 or the method of treatment of claim 2, wherein the PD-1 axis antagonist includes PD-1 antagonist, PD-L1 antagonist and PD-L2 antagonist. 6. The treatment regimen or the method of treatment of any of claim 3- 5, wherein the PD- L1 antagonist is selected from the group consisting of avelumab, BMS-936559, CA-170, durvalumab, MCLA-145, SP142, STI-A1011, STI-A1012, STI-A1010, STI-A1014 and Atezolizumab and combination thereof , preferably Atezolizumab. Attorney Reference: ONKO-003/01WO 7. A treatment regimen for treating small cell lung cancer (SCLC) in a subject, the regimen comprising administering to the subject, as separate pharmaceutical formulations, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab are administered in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 8. A method of treating small cell lung cancer (SCLC) in a subject, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Atezolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the Atezolizumab are administered to the subject in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 9. A method of enhancing immune function in a subject afflicted with small cell lung cancer, (SCLC) the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. 10. A method of treating a subject afflicted with small cell lung cancer (SCLC) with a therapeutically effective amount of Talabostat without inducing treatment-limiting side effects, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Atezolizumab. 11. The treatment regimen according to any of Claims 1, 3 and 7 or the method according to any of Claims 2, 4 and 6-10, wherein the small cell lung cancer (SCLC) is extensive stage SCLC. 12. The treatment regimen according to any of Claims 1, 3 and 7 or the method according to any of Claims 2, 4 and 6-10, wherein after cessation of treatment, the subject maintains a sustained response to progression of small cell lung cancer (SCLC). 13. The treatment regimen according to Claim 7, wherein for each treatment cycle, the Talabostat or the pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1. 14. The method according to any of Claims 8-10 wherein for each treatment cycle, the Talabostat or the pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1. Attorney Reference: ONKO-003/01WO 15. The treatment regimen according to any of Claims 1, 3 and 7 or the method according to any of Claims 2, 4 and 6-10, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered orally in one or more tablets. 16. The treatment regimen according to Claim 7 or the method according to any of Claims 6-10, wherein the Atezolizumab is administered by intravenous injection. 17. The treatment regimen according to any of Claims 1, 3 and 7 or the method according to any of Claims 2, 4 and 6-10, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.001 mg/kg to about 0.1 mg/kg. 18. The treatment regimen according to Claim 7 or the method according to any of Claims 6-10, wherein the Atezolizumab is administered at a total dose of from about 1 mg/kg to about 10 mg/kg per day. 19. The treatment regimen according to any of Claims 1, 3 and 7 or the method according to any of Claims 2, 4 and 6-10, wherein the Talabostat or the pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.4 mg to about 0.6 mg. 20. The treatment regimen according to Claim 7 or the method according to any of Claims 6-10, wherein the Atezolizumab is administered at a total dose of from about 500 mg to about 1500 mg per day. 21. The treatment regimen according to Claim 7 or the method according to any of Claims 6-10 wherein the Atezolizumab is administered at a total dose of about 1200 mg per day. 22. The treatment regimen according to any of Claim 1, 3 and 7 or the method according to any of Claims 2,4 and 6-10 wherein the total daily dose of Talabostat in cycle 1 is lower than the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in one or more subsequent cycles. 23. The treatment regimen according to Claim 7 or the method according to any of Claims 6-10, wherein the Talabostat or a pharmaceutically acceptable salt thereof and the Atezolizumab are administered to the subject in one or more treatment cycles, where each treatment cycle is of about 21 days duration, and for each treatment cycle the Talabostat or a pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1. Attorney Reference: ONKO-003/01WO 24. The treatment regimen or the method according to Claim 23, wherein the Talabostat or a pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.4 mg to about 0.6 mg. 25. The treatment regimen or the method according to Claim 24, wherein the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in cycle 1 is lower than the total daily dose of Talabostat in one or more subsequent cycles. 26. The treatment regimen according to Claim 1, 3 and 7 or the method according to any of Claims 2,4 and 6-10, wherein the Talabostat or a pharmaceutically acceptable salt thereof is Talabostat mesylate. 27. A treatment regimen for treating small cell lung cancer (SCLC) in a subject , the regimen comprising administering to the subject Talabostat mesylate and Atezolizumab in one or more treatment cycles, where each treatment cycle is of about 21 days duration, and for each treatment cycle the Talabostat is administered on each of days 1 to 14 and the Atezolizumab is administered on day 1, wherein the Talabostat mesylate is administered as one or more tablets to provide a total daily dose of Talabostat of from about 0.4 mg to about 0.6 mg and the Atezolizumab is administered as a single intravenous injection to provide a dose of from about 500 mg to about 1500 mg per day. 28. The treatment regimen or the method of any of the preceding claims, wherein the subject is administered Talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8- 14 of the first treatment cycle. 29. The treatment regimen or the method of any of the preceding claims, wherein the subject is administered Talabostat or a pharmaceutically acceptable salt thereof orally at a dose of about 0.3 mg twice daily on day 1-3 of the first treatment cycle followed by rest period of 4 days then about 03 mg twice daily on day 8-11 of the first treatment cycle. 30. A treatment regimen for treating pancreatic cancer in a subject, the regimen comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the PD-1 axis antagonist are administered in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. Attorney Reference: ONKO-003/01WO 31. A method of treating pancreatic cancer in a subject, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of PD-1 axis antagonist, wherein the Talabostat or the pharmaceutically acceptable salt thereof and the PD-1 axis antagonist are administered to the subject in oneor more treatment cycles and wherein each treatment cycle is of about 21 days duration. 32. The treatment regimen according to claim 30 or the method of treatment according to claim 31, wherein the PD-1 axis antagonist includes PD-1 antagonist, PD-L1 antagonist and PD-L2 antagonist. 33. The treatment regimen according to claim 30 or the method of treatment according to claim 31, wherein the PD-1 axis antagonist is PD-1 antagonist selected from the group consisting of BGB-A317, Pembrolizumab, MEDI0680, nivolumab, PDR001, PF-06801591, REGN-2810, SHR- 1210, TSR-042, and combination thereof 34. The treatment regimen or the method of treatment according to claim 33, wherein the PD-1 antagonist is Pembrolizumab. 35. A treatment regimen for treating pancreatic cancer in a subject, the regimen comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount Pembrolizumab, wherein the Talabostat or the pharmaceutically acceptable salt thereof and Pembrolizumab are administered in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 36. A method of treating pancreatic cancer in a subject, the method comprising administering to the subject, an effective amount of Talabostat or a pharmaceutically acceptable salt thereof and an effective amount of Pembrolizumab., wherein the Talabostat or the pharmaceutically acceptable salt thereof and the Pembrolizumab are administered to the subject in one or more treatment cycles and wherein each treatment cycle is of about 21 days duration. 37. A method of enhancing immune function in a subject afflicted with pancreatic cancer, the method comprising administering to the subject, effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. 38. A method of treating a subject afflicted with pancreatic cancer with a therapeutically effective amount of Talabostat without inducing treatment-limiting side effects, the method Attorney Reference: ONKO-003/01WO comprising administering to the subject effective amounts of Talabostat or a pharmaceutically acceptable salt thereof and Pembrolizumab. 39. The treatment regimen according to Claim 30 or 35 or the method according to any of any of Claims 31 and 36-38, wherein the pancreatic cancer is selected from a group comprising exocrine pancreatic cancer, pancreatic ductal carcinoma or adenocarcinoma of pancreas, squamous cell carcinoma, adenosquamous carcinoma, colloid carcinoma, pancreatic neuroendocrine tumors, acinar cell carcinoma, intraductal papillary-mucinous neoplasm (IPMN) or mucinous cystic neoplasm with an invasive adenocarcinoma. 40. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein after cessation of treatment the subject maintains a sustained response to progression of pancreatic cancer. 41. The treatment regimen according to Claim 35, wherein for each treatment cycle the Talabostat or a pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Pembrolizumab.is administered on day 1. 42. The method according to any of Claims 36-38, wherein for each treatment cycle the Talabostat or a pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and the Pembrolizumab.is administered on day 1. 43. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Talabostat or a pharmaceutically acceptable salt thereof is administered orally in one or more tablets. 44 The treatment regimen according to Claim35 or the method according to any of Claims 36-38, wherein the Pembrolizumab.is administered by intravenous injection. 45. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Talabostat or a pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.001 mg/kg to about 0.1 mg/kg. 46. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Pembrolizumab is administered at a total dose of from about 1 mg/kg to about 10 mg/kg per day. Attorney Reference: ONKO-003/01WO 47. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Talabostat or a pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.4 mg to about 0.6 mg. 48. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Pembrolizumab is administered at a total dose of from about 500 mg to about 1500 mg per day. 49. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Pembrolizumab is administered at a total dose of about 200 mg per day. 50. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the total daily dose of Talabostat in cycle 1 is lower than the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in one or more subsequent cycles. 51. The treatment regimen according to Claim 35 or the method according to any of Claims 36-38, wherein the Talabostat or a pharmaceutically acceptable salt thereof and the Pembrolizumab are administered to the subject in one or more treatment cycles, where each treatment cycle is of about 21 days duration, and for each treatment cycle Talabostat or a pharmaceutically acceptable salt thereof is administered on each of days 1 to 14 and Pembrolizumab is administered on day 1. 52. The treatment regimen or the method according to Claim 51, wherein the Talabostat or a pharmaceutically acceptable salt thereof is administered at a total daily dose of from about 0.4 mg to about 0.6 mg. 53. The treatment regimen or the method according to Claim 52, wherein the total daily dose of Talabostat or a pharmaceutically acceptable salt thereof in cycle 1 is lower than the total daily dose of Talabostat in one or more subsequent cycles. 54. The treatment regimen according to Claim 24 or the method according to any of Claims 25-27, wherein the Talabostat or a pharmaceutically acceptable salt thereof is Talabostat mesylate. 55. A treatment regimen for treating pancreatic cancer in a subject, the regimen comprising administering to the subject Talabostat mesylate and Pembrolizumab in one or more treatment cycles, where each treatment cycle is of about 21 days duration, and for each treatment cycle, the Talabostat is administered on each of days 1 to 14 and the Pembrolizumab is administered on day 1, wherein Talabostat mesylate is administered as one or more tablets to provide a total daily dose of Attorney Reference: ONKO-003/01WO Talabostat of from about 0.4 mg to about 0.6 mg and Pembrolizumab.is administered as a single intravenous injection to provide a dose of from about 500 mg to about 1500 mg per day. 56. The treatment regimen or the methods of any of the preceding claims, wherein the subject is administered Talabostat or a pharmaceutically acceptable salt thereof at a dose of about 0.2 mg twice daily on days 1-7 of the first treatment cycle followed by about 0.3 mg twice daily on days 8- 14 of the first treatment cycle. 57. The treatment regimen or the methods of any of the preceding claims, wherein the subject is administered Talabostat or a pharmaceutically acceptable salt thereof orally at a dose of about 0.3 mg twice daily on day 1-3 of the first treatment cycle followed by rest period of 4 days then about 03 mg twice daily on day 8-11 of the first treatment cycle.