An immune-checkpoint inhibitor, dostarlimab-gxly (Jemperli) vanishes any signs of rectal cancer in all patients in a clinical trial
June 7, 2022
By now, many people heard the incredible news about patients’ rectal cancer just vanished after a drug trial. Let’s look at the detail more carefully about the results of a phase 2 trial (NCT04165772) with a PD-1 inhibitor, dostarlimab-gxly (Jemperli) for the patients with rectal cancer which were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and published in New England Journal of Medicine (1).
A team of investigators from Memorial Sloan Kettering Cancer Center initiated a phase 2 clinical trial to evaluate whether treatment of a PD-1 inhibitor, dostarlimab-gxly (Jemperli) before the standard of care (surgery and chemotherapy) improves the outcome of rectal cancer patients. For that, the investigators treated 12 patients with stage 2 or 3 rectal cancer which lack proteins called "mismatch repair enzyme (MMRs)" in their cancer cells.
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Mismatch repair enzymes (MMRs) are responsible for correcting errors when DNA is copied during cell division.If cells lack any mismatch repair enzymes, therefore errors in DNA can not be corrected, mutations can occur, resulting in the production of abnormal proteins which may lead to the development of cancer.
Dostarlimab-gxly (Jemperli) is a type of immunotherapy called immune-checkpoint inhibitors, which target proteins called PD-1 or PD-L1, resulting in blocking the engagement of tumor cells and cytotoxic or killer T-Cells.This allows cytotoxic or killer T cells to be reactivated to kill tumor cells.For more information about immune -checkpoint inhibitors, please read our post on April 12, 2021.
After 12 patients were treated with dostarlimab-gxly (Jemperli) every 3 weeks for 6 months, they were to be followed by chemotherapy and surgery, a standard of care.However, all twelve patients did not show any sign of cancer after 6 months when tested with MRI, PET-CT, endoscopy, digital rectal examination or biopsy.Thus, no patient received no further treatments.Furthermore, no patients showed any signs of return of cancer for 24 months.None of the patients had severe side effects from dostarlimab-gxly (Jemperli).
This clinical trial result is unprecedented; however, the remarkable results are from only 12 patients. Thus, it is critical to have a confirmatory clinical trial with many more participants. In addition, only rectal cancer patients whose cancer lacks MMRs might respond to dostarlimab-gxly (Jemperli).Approximately, 5-10 % of rectal cancer cases have MMR deficiency.
Nonetheless, this study is giving us a great hope that we may be able to care for rectal cancer patients to provide longer survival, perhaps cure and better quality of life in near future.
1. Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer [published online ahead of print, 2022 Jun 5]. N Engl J Med. 2022;10.1056/NEJMoa2201445. doi:10.1056/NEJMoa2201445