On April 22, 2021, the FDA approved dostarlimab-gxly (Jemperli; GlaxoSmithKline), a PD-1 inhibitor, for the treatment of adults with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a previous platinum-containing regimen. The FDA granted dostarlimab priority review and a breakthrough therapy designation for this indication.
“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” said Richard Pazdur, MD, FDA’s Director of Oncology Center of Excellence. “This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population.”
The FDA approval of dostarlimab was based on results from the dMMR endometrial cancer cohort of the ongoing, multicenter, open-label, multicohort, phase 1 GARNET clinical trial (N = 444). Patients in the trial received intravenous dostarlimab 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Among the 71 patients with dMMR advanced or recurrent endometrial cancer who received dostarlimab in the trial, the ORR was 42.3% (12.7% complete response rate and 29.6% partial response rate). For 93% of responders, responses lasted ≥6 months.
A total of 104 patients were evaluated for safety. The most common (≥20%) adverse reactions were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common (≥2%) grade 3 or 4 adverse reactions were anemia and increased transaminase. Serious adverse reactions occurred in 34% of patients receiving dostarlimab. Serious adverse reactions in >2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia.