In remarkable early-stage human testing, a new drug that treats locally advanced rectal cancer has shown to have completely eradicated tumors in all 42 patients who took part in the Phase II trial.
The drug, Jemperli (dostarlimab-gxly), had earlier shown great potential for eliminating mismatch repair deficient (dMMR) cancers, which make up 5-10% of colorectal cancers. Following the Phase II trial, the first 24 patients assessed showed a "sustained complete clinical response" – no cancer evident – after an average of 26.3 months.
We'd emphasize that this is a small trial, and that while these early results are impressive, obviously further research is needed with a much larger cohort.
"These findings demonstrate the potential of dostarlimab-gxly as a novel approach to treating locally advanced dMMR rectal cancer that leads to durable complete tumor regression without the need for life-altering treatment," said Dr Andrea Cercek, researcher and oncologist at the Memorial Sloan Kettering Cancer Center (MSK). "As a clinician, I’ve seen firsthand the debilitating impact of standard treatment of dMMR rectal cancer and am thrilled about the potential of dostarlimab-gxly in these patients.”
The drug is a promising first-line treatment option, bypassing the need for chemotherapy and radiation. Right now, while traditional treatment is effective, it's incredibly invasive and impacts long-term quality of life. Ultimately, a third of patients currently see their cancer metastasize and become terminal.
Those who do undergo surgery often experience life-long, life-changing impacts, including bowel, urinary and sexual dysfunction, as well as secondary cancers and infertility.
“We wanted to see if we could make a tumor with the MMR(d) mutation recede and eventually disappear using only immunotherapy to spare patients these life-altering consequences of standard treatment," Dr Luis Diaz Jr said last year, after preliminary trial research showed the treatment's promise in targeting the cancer.
Unlike chemotherapy, dostarlimab-gxly is a programmed death receptor-1 (PD-1)-blocking monoclonal antibody, which enters the body and binds to the protein PD-1 T cells, encouraging these immune cells to attack cancer cells. While still in early-stage human trials, with some time before it's approved for this kind of clinical use, it's already been hyped up as a 'wonder drug' for successful, non-invasive cancer treatment.
Last year, the drug was approved by the FDA as a complementary treatment alongside chemotherapy for endometrial cancer. The pharmaceutical company behind Jemperli, GSK, will now undertake studies on other types of colorectal cancers, hoping for similarly impactful results.
“The data showing no evidence of disease in 42 patients is remarkable,” said Hesham Abdullah, GSK Senior Vice President. “These results bring us one step closer to understanding the potential of dostarlimab-gxly in this curative-intent setting for patients with dMMR locally advanced rectal cancer. We look forward to evaluating dostarlimab-gxly in certain colorectal cancers in our ongoing AZUR-1 and AZUR-2 registrational studies.”
In a statement, GSK said patients didn't experience side-effects above grade three, with most experiencing mild or moderate adverse reactions. The company noted that the drug's safety and tolerance is "consistent with the known safety profile of the agent."
The results of the long-term follow-up examinations were presented at the 2024 American Society of Clinical Oncology (ASCO) annual meeting in Chicago this week. It's worth noting that Dr. Cercek discloses a financial interest in GSK as part of the study.
Source: GSK
Editor's note: This article was updated November 13, 2024.
