FDA Expands Jemperli Approval for Advanced or Recurrent Endometrial Cancer
Key Insights
The FDA has approved Jemperli (dostarlimab-gxly) in combination with chemotherapy for adult patients with primary advanced or recurrent endometrial cancer (search).
This approval broadens the indication to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, offering a new treatment option.
The approval is based on the RUBY phase III trial, which demonstrated a statistically significant overall survival benefit in the full patient population.
The U.S. Food and Drug Administration (FDA) has expanded the approval of Jemperli (dostarlimab-gxly) in combination with carboplatin and paclitaxel (chemotherapy), followed by Jemperli as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer (search). This decision broadens the treatment's availability to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, who constitute 70-75% of endometrial cancer cases and have limited treatment options.
The approval is based on the RUBY phase III trial, which demonstrated a statistically significant overall survival (OS) benefit in the full population of patients with primary advanced or recurrent endometrial cancer (search). The trial showed a 31% reduction in the risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.
Key Findings from the RUBY Trial
At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group were alive, compared to 49% (95% CI: 43-55) in the chemotherapy group. The median overall survival (OS) was improved by 16.4 months with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.
Expert Commentary
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, stated, "Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer (search) regardless of biomarker status... We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumors where treatment options have been limited."
Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial, added, "The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer (search) and today’s expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer."
About the RUBY Trial
The RUBY trial is a two-part, global, randomized, double-blind, multi-center phase III trial involving patients with primary advanced or recurrent endometrial cancer (search). Part 1 evaluated dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly versus carboplatin-paclitaxel plus placebo followed by placebo. The dual-primary endpoints were investigator-assessed PFS and OS. Part 2 is evaluating dostarlimab-gxly plus carboplatin-paclitaxel followed by dostarlimab-gxly plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.
Safety Profile
The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy, and vomiting.
Endometrial Cancer Context
Endometrial cancer (search) is the most common gynecologic cancer in developed countries, with an estimated 1.6 million people living with active disease worldwide. Incidence rates are projected to increase by approximately 40% between 2020 and 2040. Approximately 15-20% of patients are diagnosed with advanced disease at the time of diagnosis, and among these, 70-75% have MMRp/MSS tumors.