European Commission Approves GSK's Jemperli Plus Chemotherapy for Advanced Endometrial Cancer
Key Insights
The European Commission has approved Jemperli (dostarlimab) in combination with chemotherapy for first-line treatment of advanced or recurrent endometrial cancer (search).
The approval expands the indication to include patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors, representing approximately 75% of cases.
The RUBY trial demonstrated a 31% reduction in the risk of death with Jemperli plus chemotherapy compared to chemotherapy alone, with a median OS of 44.6 months.
The European Commission has approved GSK's Jemperli (dostarlimab) in combination with chemotherapy (carboplatin and paclitaxel) for the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer (search) who are candidates for systemic therapy. This decision broadens the previous European Union (EU) indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, which constitute approximately 75% of endometrial cancer cases. The expanded approval marks a significant advancement in the treatment landscape, offering an immuno-oncology-based option for a broader patient population.
The approval is based on the results from Part 1 of the Phase III RUBY trial, a global, randomized, double-blind, multicenter study. The RUBY trial is the only clinical trial in this setting to demonstrate a clinically meaningful and statistically significant overall survival (OS) benefit in the full population of patients with primary advanced or recurrent endometrial cancer (search). The study demonstrated 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 analysis, the probability of survival was 61% (95% CI: 54-67) for patients in the Jemperli plus chemotherapy group (245 patients) compared to 49% (95% CI: 43-55) in the chemotherapy group (249 patients). The median overall survival (OS) was 44.6 months (95% CI: 32.6-Not Reached) in the Jemperli plus chemotherapy arm versus 28.2 months (95% CI: 22.1-35.6) in the chemotherapy alone arm, representing a 16.4-month improvement in median OS.
"For the first time, all patients with primary advanced or recurrent endometrial cancer (search) in the EU have an approved immuno-oncology-based treatment that has shown a statistically significant and clinically meaningful overall survival benefit," said Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK.
Dr. Mansoor Raza Mirza, Chief Oncologist at Copenhagen University Hospital in Denmark and the principal investigator of the RUBY trial, added, "Clinicians have been waiting for years for an immuno-oncology-based option that can meaningfully improve overall survival outcomes for patients with MMRp/MSS primary advanced or recurrent endometrial cancer (search). The expanded approval represents a significant advance that delivers on this hope, now for patients with both dMMR/MSI-H and MMRp/MSS tumours."
Safety and Tolerability
The safety and tolerability profile for Jemperli combined with carboplatin-paclitaxel was consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse reactions (≥ 10%) in patients receiving Jemperli plus chemotherapy were rash, maculopapular rash, hypothyroidism, pyrexia, increased alanine aminotransferase, increased aspartate aminotransferase, and dry skin.
Endometrial Cancer Landscape
Endometrial cancer (search), originating in the inner lining of the uterus, is the most common gynecologic cancer in developed countries. Approximately 1.6 million people are living with active disease at any stage, with 417,000 new cases reported each year worldwide. Incidence rates are projected to increase by approximately 40% between 2020 and 2040. In Europe, an estimated 121,000 people are diagnosed with primary advanced or recurrent endometrial cancer annually. Among these patients, approximately 75% have MMRp/MSS tumors.
About Jemperli (dostarlimab)
Jemperli is a programmed death receptor-1 (PD-1 (search))-blocking antibody. In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer (search), including those with MMRp/MSS and dMMR/MSI-H tumors. It is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen and who are not candidates for curative surgery or radiation. Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc.