On February 9, 2023, the FDA granted regular approval to dostarlimab-gxly (Jemperli; GlaxoSmithKline), a PD-1 inhibitor, for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, whose disease progressed during or after treatment with a previous platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation.
This latest FDA approval converts the agent’s initial April 2021 accelerated approval to full approval. The April 2021 approval made dostarlimab the first FDA-approved immunotherapy for dMMR advanced endometrial cancer.
Dostarlimab was also previously approved for adult patients with dMMR recurrent or advanced solid tumors whose disease progressed during or after previous treatment and who have no satisfactory alternative treatment options.
The conversion to regular approval was based on additional results from the phase 1 GARNET study (NCT02715284), a multicenter, multicohort, open-label, clinical trial of patients with advanced solid tumors, including an efficacy population of 141 patients with dMMR recurrent or advanced endometrial cancer that progressed during or after a platinum-containing regimen. Patients were excluded from the trial if they had received PD-1/PD-LI–blocking antibodies, other immune checkpoint inhibitors, or had autoimmune diseases requiring systemic immunosuppressant agents within 2 years.
The major efficacy measures included overall response rate (ORR) and duration of response (DOR). The confirmed ORR was 45.4% (95% confidence interval, 37.0-54.0); in addition, 15.6% achieved a complete response and 29.8% had a partial response. The median DOR was not reached: 85.9% of patients had a DOR ≥12 months, and 54.7% of patients had a DOR ≥24 months (range, 1.2+ to 52.8+).
The most common (≥20%) adverse events were fatigue/asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. Immune-mediated adverse events can occur, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions.
The recommended dostarlimab-gxly dose and schedule (doses 1-4) is 500 mg every 3 weeks. Subsequent dosing, beginning 3 weeks after dose 4, is 1000 mg every 6 weeks until disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered as an intravenous infusion over 30 minutes.