Dostarlimab (Jemperli; GlaxoSmithKline LLC) has displayed statistically significant overall survival (OS) and progression-free survival (PFS) results among patients with primary advanced or recurrent endometrial cancer in the RUBY phase 3 trial, according to GlaxoSmithKline (GSK).
Takeaways
- Dostarlimab, in combination with carboplatin and paclitaxel, shows statistically significant improvements in overall survival (OS) and progression-free survival (PFS) for patients with primary advanced or recurrent endometrial cancer, as per the RUBY phase 3 trial results.
- The study, conducted globally and in 2 parts, included a diverse population, including histologies often excluded from clinical trials, thus providing robust data on efficacy and safety.
- Part 1 of the trial compared dostarlimab plus chemotherapy to chemotherapy alone, demonstrating a 31% reduction in the risk of death and a significant improvement in median OS.
- Part 2 of the trial showed a 40% reduction in the risk of disease progression or death with dostarlimab plus chemotherapy compared to placebo, along with significant improvements in median PFS, particularly in patients with mismatch repair proficient/microsatellite stable tumors.
- The safety profiles of dostarlimab regimens were consistent with known profiles of individual medicines, with manageable adverse events reported, indicating both safety and efficacy in treating primary advanced or recurrent endometrial cancer.
Dostarlimab is a programmed death receptor-1 indicated alongside carboplatin and paclitaxel to treat adult US patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient. The combination therapy has received Breakthrough Therapy designation and Priority Review from the FDA.
The efficacy of dostarlimab was evaluated in the 2-part, global, randomized, double-blind, multicenter phase 3 RUBY trial. In part 1, dostarlimab plus carboplatin-paclitaxel followed by dostarlimab was compared to carboplatin-paclitaxel plus placebo followed by placebo.
Part 1 assessed PFS using Response Evaluation Criteria in Solid Tumours v1.1 and OS. Participants were recruited from a broad population, including histologies often excluded from clinical trials.
In part 2, the placebo regimen was compared to dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib (Zejula; Zai Lab). Part 2 assessed PFS in the overall population followed by patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors. OS was evaluated as a secondary endpoint.
Safety profiles of both dostarlimab regimens remained consistent with known safety profiles of the individual medicines. Additionally, statistically significant efficacy results were reported. In part 1, the risk of death was reduced by 31%, with a hazard ratio (HR) of 0.69.
Median OS was also significantly improved in the overall population, at 44.6 months vs 28.2 months. In the MMRp/MSS cohort, the risk of death was reduced by 21% and the median OS was 34 months vs 27 months.
A 12% increase in grade 3 or higher serious treatment-emergent adverse events (AEs) were reported in the treatment arm vs the control arm. Discontinuation because of treatment-emergent adverse events was reported in 19.1% and 8.1%, respectively.
In part 2, the risk of disease progression or death was reduced by 40% in the treatment arm, with an HR of 0.60. The median PFS improved at 14.5 months vs 8.3 months.
In the MMRp/MSS cohort, the risk of disease progression or death was reduced by 37%, and the median PFS was 14.3 months vs 8.3 months. Overall, discontinuation because of a treatment-emergent AE was reported in 15.7% of the treatment arm vs 4.2% of the control arm.
These results indicated safety and efficacy from dostarlimab in patients with primary advanced or recurrent endometrial cancer. GSK expects the FDA to grant the drug regulatory submission acceptance based on this data.
Reference
Positive RUBY phase III data show potential for Jemperli (dostarlimab) combinations in more patients with primary advanced or recurrent endometrial cancer. GSK. March 16, 2024. Accessed March 21, 2024. https://www.gsk.com/en-gb/media/press-releases/positive-ruby-phase-iii-data-show-potential-for-jemperli-dostarlimab-combinations-in-more-patients-with-primary-advanced-or-recurrent-endometrial-cancer/
