FDA Approves Dostarlimab for Mismatch Repair Deficient Recurrent or Advanced Endometrial Cancer

On February 9, 2023, the US Food and Drug Administration (FDA) granted full approval to dostarlimab-gxly for adult patients with mismatch repair deficient recurrent (dMMR) recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen. Dostarlimab had received accelerated approval for the same patient population in April 2021.

This full approval was based on results from the multicenter, multicohort, open-label GARNET trial conducted in patients with advanced solid tumors. The trial enrolled 141 patients with dMMR recurrent or advanced endometrial cancer who had progressed on or after a platinum-based chemotherapy. Patients were excluded if they had been treated with prior PD-1/PD-L1-blocking antibodies, other immune checkpoint inhibitors, or had autoimmune diseases requiring systemic immunosuppressant agents within 2 years.

The study’s major efficacy outcomes were overall response rate (ORR) and duration of response (DOR). Confirmed ORR was 45.4% (95% confidence interval [CI], 37 to 54), with a 15.6% complete response rate and a 29.8% partial response rate. Median DOR was not reached, with 85.9% of patients experiencing durations of response ≥12 months and 54.7% of patients experiencing durations of response ≥24 months (range: 1.2+ to 52.8+.

The most common adverse reactions, occurring in ≥20% of patients, included fatigue/asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. Additionally, there is the potential for immune-mediated adverse reactions such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.

The recommended dosage and schedule of dostarlimab-gxly is 500 mg administered via 30-minute intravenous infusion every 3 weeks for doses 1 through 4. Further treatment should begin 3 weeks after dose 4, at which point the recommended dose and schedule is 1000 mg every 6 weeks until disease progression or unacceptable toxicity.

Source:

FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. United States Food and Drug Administration. February 9, 2023. Accessed January 30, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-endometrial-cancer