FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer
Regulatory approval news: On Feb 9, 2023, the FDA approved dostarlimab-gxly (Jemperli) for adults with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer, determined by an FDA-approved test, after progression on/after a prior platinum-containing regimen and not candidates for curative surgery or radiation. Regular approval was supported by the single-arm GARNET trial (NCT02715284), with confirmed ORR 45.4% and median duration of response not reached.
FDA approval (Feb 9, 2023)
The US Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli; GlaxoSmithKline LLC) for adult patients with 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.
The FDA noted that dostarlimab-gxly previously received accelerated approval (April 2021) in a similar dMMR endometrial cancer population after platinum therapy.
Supporting evidence
Regular approval was evaluated in GARNET (NCT02715284), a multicenter, multicohort, open-label trial in advanced solid tumors. The efficacy cohort included 141 patients with dMMR recurrent or advanced endometrial cancer progressing on/after platinum therapy. Key exclusions included prior PD-1/PD-L1–blocking antibodies or other immune checkpoint inhibitors, and autoimmune disease requiring systemic immunosuppression within 2 years.
Primary outcomes were ORR and DOR by blinded independent central review (RECIST v1.1):
- Confirmed ORR: 45.4% (95% CI, 37.0–54.0)
- Complete response: 15.6%; partial response: 29.8%
- Median DOR: not reached; 85.9% had DOR ≥12 months and 54.7% ≥24 months (range 1.2+ to 52.8+)
Safety and dosing (label highlights)
Common adverse reactions (≥20%) included fatigue/asthenia, anemia, rash, nausea, diarrhea, constipation, and vomiting. Immune-mediated adverse reactions can occur (eg, pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin reactions). Recommended dosing: 500 mg IV q3w (cycles 1–4), then 1,000 mg IV q6w starting 3 weeks after dose 4, until progression or unacceptable toxicity.