FDA Accepts sBLA for Dostarlimab With Chemotherapy to Treat Endometrial Cancer


Dostarlimab plus chemotherapy is the only immuno-oncology-based therapy that showed statistically significant and clinically meaningful survival benefit in the overall patient population.

Peach ribbon for endometrial cancer awareness -- Image credit: Chinnapong | stock.adobe.com

Image credit: Chinnapong | stock.adobe.com

About the Trial

Trial Name: A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer (RUBY)

ClinicalTrials.gov ID: NCT03981796

Sponsor: Tesaro, Inc.

Completion Date (Estimated): November 26, 2026

The FDA has accepted the supplemental biologics license application (sBLA) for dostarlimab (Jemperli; GlaxoKlineSmith) in combination with standard of care chemotherapy, either carboplatin or paclitaxel, for the treatment of endometrial cancer. The sBLA will expand treatment to all adult patients who have primary advanced or recurrent endometrial cancer, and this includes those with mismatch repair proficient (MMRp) or microsatellite stable (MSS) tumors.1

Dostarlimab is a programmed death receptor 1 (PD-1)-blocking antibody that binds to the PD-1 receptor. Previously, it was approved by the FDA to be used in combination with carboplatin and paclitaxel, followed by dostarlimab as a monotherapy, in adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test or microsatellite instability high (MSI-H).1,2

The sBLA comes after positive results from part 1 of the phase 3 RUBY trial (NCT03981796). The 2-part, global, randomized, double-blind, multicenter trial evaluated patients with primary advanced or recurrent endometrial cancer. Part 1 evaluates dostarlimab plus carboplatin-paclitaxel, followed by dostarlimab vs carboplatin-paclitaxel plus placebo, followed by placebo. The dual primary end points are investigator-assessed progression-free survival (PFS) and overall survival (OS). Part 2 evaluates dostarlimab plus carboplatin-paclitaxel, followed by dostarlimab plus niraparib vs placebo plus carboplatin-paclitaxel, followed by placebo. The primary end point is investigator-assessed PFS in the studied population, as well as PFS in the MMRp/MSS population, and the key secondary end point is OS in the overall population.1

According to the investigators, dostarlimab plus chemotherapy had demonstrated both statistically significant and clinically meaningful OS and PFS in parts 1 and 2, respectively. Part 1 demonstrated that, compared with chemotherapy alone, dostarlimab plus chemotherapy had reduced the risk of death by approximately 31%, and patients had a median OS of about 16.4 months. Additionally, the MMRp/MSS population who received the dostarlimab regimen had their risk of death reduced by approximately 21% and an improvement in OS by a median of 7 months. The first part of the RUBY trial is the only clinical trial to demonstrate a statistically significant survival benefit in the overall patient population.1,3

“The positive data presented today further show how dostarlimab-based regimens could benefit a broader set of patients with endometrial cancer. The results we’ve seen to date comprise the growing body of evidence supporting the role of dostarlimab as the backbone of our immuno-oncology development program,” said Hesham Abdullah, MD, MSc, senior vice president and global head of oncology and research and development at GSK, said in the press release. “Our goal is to continue to identify ways to use dostarlimab alone and in combination with other therapies to help improve outcomes for patients with limited treatment options.”3

In the dostarlimab group, grade 3 or higher as well as treatment-emergent adverse events (AEs) were about 12% higher compared with those who received placebo plus chemotherapy. Additionally, any-grade AEs in other research studying dostarlimab include fatigue, alopecia, nausea, peripheral neuropathy, anemia, constipation, diarrhea, reduced appetite, rash, among others. The investigators note that the safety profile for the dostarlimab combination is consistent with the known safety profiles from the individual agents.1-3

“I celebrate the practice-changing potential of adding [dostarlimab] to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options," said principal trial investigator Matthew Powell, MD, chief of the Division of Gynecologic Oncology at Washington University School of Medicine, in a press release. "Based on the results from the RUBY clinical trial, I look forward to the addition of [dostarlimab] to chemotherapy becoming a new standard of care for patients.”2

1. GlaxoKlineSmith. US FDA accepts for priority review GSK’s application for an expanded indication of Jemperli (dostarlimab) plus chemotherapy to include all adult patients with primary advanced or recurrent endometrial cancer. News release. April 24, 2024. Accessed April 25, 2024. https://www.gsk.com/en-gb/media/press-releases/fda-accepts-gsk-application-expanded-indication-of-jemperli-dostarlimab-plus-chemotherapy-include-all-adult-patients-primary-advanced-recurrent-endometrial-cancer/
2. FDA Approves Dostarlimab Combination for Primary Advanced or Recurrent Endometrial Cancer.Pharmacy Times. August 1, 2023. Accessed April 25, 2024. https://www.pharmacytimes.com/view/fda-approves-dostarlimab-combination-for-primary-advanced-or-recurrent-endometrial-cancer
3. Gallagher, A. Dostarlimab Plus Chemotherapy Demonstrates Significant Overall Survival Benefit in Endometrial Cancer. Pharmacy Times. April 2, 2024. Accessed April 15, 2024. https://www.pharmacytimes.com/view/dostarlimab-plus-chemotherapy-demonstrates-significant-overall-survival-benefit-in-endometrial-cancer
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