FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy

On August 1, 2024, the Food and Drug Administration 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). Dostarlimab-gxly previously was approved with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent EC that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).

Full prescribing information for Jemperli will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial conducted in 494 patients with primary advanced or recurrent EC. Patients were randomized (1:1) to either dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly, or placebo with carboplatin and paclitaxel, followed by placebo. Chemotherapy regimens are described in the above link for full prescribing information. Randomization was stratified by mismatch repair (MMR)/microsatellite instability (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) (investigator-assessed 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% 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=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 (Hazard Ratio=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 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-gxly were similar to those previously reported for dostarlimab-gxly. See dostarlimab-gxly full prescribing information for complete adverse reactions.

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.

Expedited Programs

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. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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