On February 9, the U.S. Food and Drug Administration (FDA) approved the monoclonal antibody dostarlimab-gxly (Jemperli) for adult patients with mismatch repair–deficient (dMMR), recurrent or advanced endometrial cancer, as determined by an FDA-approved test, whose disease has progressed on or following a prior platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation.
In April 2021, dostarlimab-gxly received accelerated approval for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen.
GARNET Trial
Efficacy for the regular approval was evaluated in GARNET (ClinicalTrials.gov identifier: NCT02715284), a multicenter, multicohort, open-label trial conducted in patients with advanced solid tumors. The efficacy population consisted of a cohort of 141 patients with dMMR recurrent or advanced endometrial cancer who had progressed on or after a platinum-containing regimen. Patients treated with prior PD-1/PD-L1–blocking antibodies or other immune checkpoint inhibitors, or who had autoimmune diseases requiring systemic immunosuppressant agents within 2 years, were excluded.
The major efficacy outcome measures were overall response rate and duration of response as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1. Confirmed overall response rate was 45.4% (95% confidence interval = 37.0%–54.0%), with a 15.6% complete response rate and a 29.8% partial response rate. Median duration of response was not reached, with 85.9% of patients having durations lasting 12 months or longer and 54.7% of patients having durations lasting 24 months or longer (range = 1.2+ to 52.8+).
The most common adverse reactions (in ≥ 20% of patients receiving dostarlimab) were fatigue/asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. Immune-mediated adverse reactions can occur when taking the agent, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.
The recommended dostarlimab-gxly dose and schedule (doses 1 through 4) is 500 mg every 3 weeks. Subsequent dosing—beginning 3 weeks after dose 4—is 1,000 mg every 6 weeks until disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered as an intravenous infusion over 30 minutes.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.
