On 1 August 2024, the US Food and Drug Administration (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. Dostarlimab-gxly previously was approved with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).
Efficacy was evaluated in RUBY (NCT03981796), a randomised, multicentre, double-blind, placebo-controlled study conducted in 494 patients with primary advanced or recurrent endometrial cancer. Patients were randomised (1:1) to either dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly, or placebo with carboplatin and paclitaxel, followed by placebo. Randomisation was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV).
The major efficacy outcome measures were progression-free survival (PFS) by investigator-assessment using RECIST v1.1 in the dMMR/MSI-H and overall populations, and overall survival (OS) in the overall population. In the overall population, a statistically significant OS improvement was observed with a median OS of 44.6 months (95% confidence interval [CI] 32.6, not reached) and 28.2 months (95% CI 22.1, 35.6) in the dostarlimab-gxly and placebo arms, respectively (hazard ratio [HR] 0.69, 95% CI 0.54, 0.89; 1-sided p-value = 0.002). Median PFS in the overall population was 11.8 months (95% CI 9.6, 17.1) and 7.9 months (95% CI 7.6, 9.5) in the dostarlimab-gxly and placebo arms, respectively (HR 0.64, 95% CI 0.51, 0.80; 1-sided p-value < 0.0001).
The most common adverse reactions (≥20%) with dostarlimab-gxly with carboplatin and paclitaxel were anaemia, 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, diarrhoea, decreased albumin, abdominal pain, dyspnoea, decreased appetite, increased amylase, urinary tract infection and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported for dostarlimab-gxly.
The recommended dostarlimab-gxly dose is 500 mg every 3 weeks for 6 cycles with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. Dostarlimab-gxly 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 granted priority review.
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