FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy
Regulatory approval: On Aug 1, 2024, the FDA approved dostarlimab-gxly (Jemperli) with carboplatin/paclitaxel followed by dostarlimab monotherapy for adult patients with primary advanced or recurrent endometrial cancer, expanding beyond the prior dMMR/MSI-H–restricted indication. Approval was supported by the phase 3 RUBY trial (N=494), which showed statistically significant improvements in overall survival and progression-free survival in the overall population versus placebo plus chemotherapy.
FDA approval expands dostarlimab-gxly use in endometrial cancer
Type: Regulatory approval (FDA)
Date: 2024-08-01
On August 1, 2024, the FDA approved dostarlimab-gxly (Jemperli; GSK) with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adult patients with primary advanced or recurrent endometrial cancer (EC). Previously, dostarlimab-gxly with carboplatin/paclitaxel followed by dostarlimab was approved for primary advanced or recurrent EC that is dMMR or MSI-H.
Supporting evidence (RUBY; NCT03981796)
Efficacy was evaluated in RUBY, a randomized, multicenter, double-blind, placebo-controlled trial in 494 patients with primary advanced or recurrent EC. Patients were randomized 1:1 to dostarlimab-gxly plus carboplatin/paclitaxel followed by dostarlimab-gxly, or placebo plus carboplatin/paclitaxel followed by placebo. Stratification included MMR/MSI status, prior external pelvic radiotherapy, and disease status.
In the overall population, FDA reported:
- Overall survival (OS): median 44.6 vs 28.2 months (HR 0.69; 95% CI 0.54–0.89; 1-sided p=0.002)
- Progression-free survival (PFS): median 11.8 vs 7.9 months (HR 0.64; 95% CI 0.51–0.80; 1-sided p<0.0001)
Safety and dosing (high level)
Common adverse reactions (≥20%) included anemia, increased creatinine, peripheral neuropathy, fatigue, nausea, alopecia, cytopenias, LFT abnormalities, arthralgia, rash, diarrhea/constipation, abdominal pain, dyspnea, UTI, and vomiting. Immune-mediated adverse reactions were described as similar to prior reports.
Recommended dosing: 500 mg Q3W x6 with chemotherapy, then 1,000 mg Q6W monotherapy until progression/unacceptable toxicity or up to 3 years; administer dostarlimab before chemotherapy on the same day.