GSK plc (LON/NYSE: GSK) has announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of Jemperli (dostarlimab) in combination with carboplatin-paclitaxel (chemotherapy), for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy. The CHMP opinion is one of the final steps prior to a marketing authorisation decision by the European Commission.
· If approved, dostarlimab would become the first new frontline treatment option in the European Union (EU) in decades and the only immuno-oncology combination regimen available for this patient population with high unmet need
· Decision on EU marketing authorisation expected by the end of the year
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “We are pleased with this positive CHMP opinion and the potential for dostarlimab with chemotherapy to treat patients with this very challenging form of endometrial cancer. If approved, dostarlimab plus chemotherapy will be the first new treatment option in decades for these patients in the European Union, offering long-awaited new hope for improved long-term outcomes. This opinion further reinforces our confidence in dostarlimab’s important role in the immuno-oncology treatment landscape.”
GSK’s application for the authorisation of dostarlimab is based on interim analysis results from Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial, which were presented (https://www.gsk.com/en-gb/media/press-releases/phase-iii-ruby-clinical-trial-demonstrates-potential-of-jemperli-plus-chemotherapy-to-redefine-the-treatment-of-primary-advanced-or-recurrent-endometrial-cancer/) at the European Society for Medical Oncology (ESMO) Virtual Plenary and Society of Gynecologic Oncology (SGO) Annual Meeting on 27 March 2023, and simultaneously published in The New England Journal of Medicine. The trial results reflect a robust median duration of follow-up of ≥ 25 months. Part 1 of the RUBY trial met its primary endpoint of investigator-assessed progression-free survival (PFS) in patients treated with dostarlimab plus carboplatin and paclitaxel in the dMMR/MSI-H population. In the dMMR/MSI-H population, a 72% reduction in the risk of disease progression or death was observed (HR: 0.28 [95% CI: 0.16-0.50]).
In a prespecified, exploratory analysis of overall survival (OS) in the dMMR/MSI-H population, the addition of dostarlimab to chemotherapy resulted in a 70% reduction in the risk of death relative to chemotherapy alone (HR: 0.30 [95% CI: 0.13-0.70]).
The safety and tolerability profile for dostarlimab plus carboplatin and paclitaxel was generally consistent with the known safety profiles of the individual agents. The most common adverse reactions (≥ 10%) in patients receiving dostarlimab plus chemotherapy were rash, hypothyroidism (overactive thyroid), increased alanine aminotransferase or increased aspartate aminotransferase (increased liver enzyme levels in the blood), pyrexia (fever) and dry skin.
This opinion follows the July 2023 expansion of the label for Jemperli in the US to include this indication (https://www.gsk.com/en-gb/media/press-releases/jemperli-plus-chemotherapy-approved-in-us-for-new-indication/). The new indication for Jemperli 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, Jemperli was also approved in the United Kingdom earlier this month in combination with platinum-containing chemotherapy for the treatment of adult patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and who are candidates for systemic therapy. The application remains under review in Australia, Canada, Switzerland and Singapore.
In the EU, Jemperli currently has conditional approval as a monotherapy for treating adult patients with dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen. If the European Commission approves the frontline indication for Jemperli + chemotherapy, this conditional approval is expected to be converted to full approval at the same time. A decision is expected by the end of this year.
