Dostarlimab (brand name Jemperli) has been granted marketing authorisation by the European Commission (EC) in combination with carboplatin-paclitaxel (chemotherapy) for certain types of endometrial cancer, its manufacturer GSK has announced.
It is the first and only frontline immuno-oncology treatment in the European Union (EU) for 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 authorisation also converts the EC’s previous conditional approval of dostarlimab to a full 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.
Dostarlimab is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.
Dr Mansoor Raza Mirza, chief oncologist, Copenhagen University Hospital, Denmark, said: ’Today’s European Commission approval is welcomed news as I believe it will define a new standard of care for certain patients with advanced or recurrent endometrial cancer in the EU.’
Practice-changing potential of dostarlimab
The EC authorisation of dostarlimab is based on interim analysis results from the two-part global, randomised, double-blind, multicentre phase 3 trial RUBY.
The dual-primary endpoints in Part 1 were investigator-assessed progression-free survival (PFS) based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS.
The trial met its primary endpoint of investigator-assessed PFS, demonstrating a statistically significant and clinically meaningful benefit in patients treated with dostarlimab plus carboplatin and paclitaxel in the dMMR/MSI-H population.
A 72% reduction in the risk of disease progression or death was observed relative to chemotherapy alone (HR: 0.28 [95% CI: 0.16-0.50]).
In a prespecified, exploratory analysis of 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 (underactive thyroid), increased alanine aminotransferase or increased aspartate aminotransferase (increased liver enzyme levels in the blood), pyrexia (fever) and dry skin.
Dr Mirza, the RUBY trial’s principal investigator, commented: ’The results from the RUBY trial, which led to this approval, underscore the practice-changing potential of dostarlimab for these patients.’