The US Food and Drug Administration (FDA) has approved GSK’s Jemperli (dostarlimab) 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 that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).
The supplemental Biologics License Application (sBLA) supporting this new indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.
Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: “Today’s expanded approval of Jemperli redefines the treatment landscape for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression.
“In the RUBY trial, Jemperli plus chemotherapy demonstrated a 71% reduction in the risk of disease progression or death versus chemotherapy in this patient population, providing a statistically significant and clinically meaningful benefit. These results and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”
With this approval, Jemperli is now indicated earlier in treatment in combination with chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. Jemperli is already approved in the US as monotherapy in adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.
Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: “As a clinician, I celebrate the practice-changing potential of adding Jemperli to chemotherapy for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer who have had limited treatment options. Based on the results from the RUBY clinical trial, I look forward to the addition of Jemperli to chemotherapy becoming a new standard of care for patients.”
Wenora Johnson, President, Board of Directors, Facing Our Risk of Cancer Empowered (FORCE) said: “The endometrial cancer community is thrilled by today’s news, which changes the treatment paradigm for a population with long-term unmet needs. FORCE is grateful for the many participants and researchers who contributed to this important study. As an endometrial cancer survivor, I know how much this approval offers hope for patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer.”
The FDA approval is supported by interim analysis results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial, which reflect a robust median duration of follow-up of ≥ 25 months. The trial met the primary endpoint of investigator-assessed progression-free survival (PFS), demonstrating a statistically significant and clinically meaningful benefit in patients treated with Jemperli plus carboplatin and paclitaxel in the dMMR/MSI-H population. In the dMMR/MSI-H population, a 71% reduction in the risk of disease progression or death was observed. Part 1 of the RUBY trial continues to assess overall survival (OS) in the intent-to-treat (ITT) population, a dual-primary endpoint alongside investigator-assessed PFS.
The safety and tolerability profile for Jemperli plus carboplatin and paclitaxel 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 rash, diarrhoea, hypothyroidism and hypertension.
The RUBY trial data were presented at the European Society for Medical Oncology (ESMO) Virtual Plenary and Society of Gynecologic Oncology (SGO) Annual Meeting on 27 March 2023, and were simultaneously published in The New England Journal of Medicine.
The sBLA supporting this new indication was reviewed under the FDA Oncology Center of Excellence Project Orbis Framework, which allowed for concurrent submission to and review by US and other international regulatory authorities. As part of Project Orbis, the application remains under review in Australia, Canada, Switzerland, Singapore and the United Kingdom. A marketing authorisation application is also under review by the European Medicines Agency.