On August 1, the U.S. Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for adults with primary advanced or recurrent endometrial cancer.
Dostarlimab was previously approved in July 2023 with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H).
RUBY Trial
Efficacy was evaluated in RUBY (ClinicalTrials.gov identifier NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial conducted in 494 patients with primary advanced or recurrent endometrial cancer. Patients were randomly assigned 1:1 to receive dostarlimab with carboplatin and paclitaxel followed by dostarlimab or placebo with carboplatin and paclitaxel followed by placebo. Random assignment was stratified by MMR/MSI status, receipt of prior external pelvic radiotherapy, and disease status (recurrent, primary stage III, or primary stage IV).
The major efficacy outcome measures were progression-free survival (investigator-assessed using Response Evaluation Criteria in Solid Tumors version 1.1) in the dMMR/MSI-H and overall populations and overall survival in the overall population. In the overall population, a statistically significant overall survival improvement was observed, with a median overall survival of 44.6 months (95% confidence interval [CI] = 32.6 months to not reached) and 28.2 months (95% CI = 22.1–35.6 months) in the dostarlimab and placebo arms, respectively (hazard ratio [HR] = 0.69, 95% CI = 0.54–0.89, one-sided P = .002). Median progression-free survival in the overall population was 11.8 months (95% CI = 9.6–17.1 months) and 7.9 months (95% CI = 7.6–9.5 months) in the dostarlimab and placebo arms, respectively (HR = 0.64, 95% CI = 0.51–0.80, one-sided P < .0001).
The most common adverse reactions occurring in at least 20% of patients treated with dostarlimab with carboplatin and paclitaxel were anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab were similar to those previously reported for the agent.
The recommended dostarlimab dose is 500 mg every 3 weeks for six cycles with carboplatin and paclitaxel, followed by 1,000 mg of monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. Dostarlimab should be administered before chemotherapy when administered on the same day.
This review used the Assessment Aid, a voluntary submission from the applicant, to facilitate the FDA’s assessment. The FDA approved this application 3 weeks ahead of the FDA goal date. This application was also granted Priority Review.
