Dostarlimab/Chemotherapy Under EMA Review for Primary Advanced/Recurrent Endometrial Cancer

The European Medicines Agency (EMA) has accepted for review an application to expand the indication for dostarlimab-gxly (Jemperli) plus standard carboplatin and paclitaxel to all adult patients with primary advanced or recurrent endometrial cancer.¹

This application was based on findings from part 1 of the phase 3 RUBY trial (NCT03981796), in which the combination elicited statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits in the overall population of patients who received dostarlimab plus chemotherapy vs those given chemotherapy alone. At the second interim analysis, with OS data at 51% maturity, the combination reduced the risk of death by 31% vs placebo plus chemotherapy (HR, 0.69; 95% CI, 0.54-0.89; stratified log-rank P = .0020).² The median OS was 44.6 months in the dostarlimab arm (n = 245) vs 28.2 months in the placebo arm (n = 249).

In the prespecified exploratory OS analysis in the mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) population, with OS data at 40% maturity, dostarlimab plus chemotherapy lowered the risk of death vs placebo plus chemotherapy (HR, 0.32; 95% CI, 0.17-0.63; nominal P = .0002). The median OS was not yet reached (NR) vs 31.4 months in the dostarlimab (n = 53) and placebo (n = 65) arms, respectively.

In the prespecified exploratory OS analysis in the MMR-proficient (pMMR)/microsatellite stable (MSS) population, with OS data at 55% maturity, a trend favoring OS was observed for dostarlimab plus chemotherapy (HR, 0.79; 95% CI, 0.60-1.04; nominal P = .0493). The median OS was 34.0 vs 27.0 months in the dostarlimab (n = 192) and placebo (n = 184) arms, respectively.

Regarding PFS, prior data from the first interim analysis showed that dostarlimab plus chemotherapy reduced the risk of progression or death vs placebo plus chemotherapy by 36% in the overall population (HR, 0.64; 95% CI, 0.51-0.80; P < .0001) and by 72% in the dMMR/MSI-H population (HR, 0.28; 95% CI, 0.16-0.50; P < .0001).

Updated data for time to second progression (PFS2) showed that in the overall population, the dostarlimab regimen led to a median PFS2 of 32.3 months vs 18.4 months for chemotherapy alone (HR, 0.66; 95% CI, 0.52-0.84; stratified log-rank P = .0020). In the dMMR/MSI-H population, dostarlimab plus chemotherapy lowered the risk of progression or death on the first subsequent anticancer therapy vs placebo plus chemotherapy (HR, 0.33; 95% CI, 0.18-0.63). The median PFS2 was not reached vs 21.6 months in the dostarlimab and placebo arms, respectively.

In the pMMR/MSS population, fewer patients in the dostarlimab plus chemotherapy arm had experienced progression or death vs placebo plus chemotherapy (HR, 0.74; 95% CI, 0.57-0.97). The median PFS2 was 24.6 vs 15.9 months in the dostarlimab and placebo arms, respectively.

The safety and tolerability profiles of dostarlimab plus chemotherapy in RUBY were generally consistent with the known safety profiles of the individual drugs.¹

The EMA’s Committee for Medicinal Products for Human Use will start the formal review process to make a recommendation to the European Commission. The potential European approval of this combination for this indication is expected in the first half of 2025.

In the European Union (EU), dostarlimab plus carboplatin and paclitaxel is currently approved for the treatment of adult patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer who are candidates for systemic therapy. The approval of this new application would extend the use of this combination to all patients with primary advanced or recurrent endometrial cancer, regardless of biomarker type, including those with pMMR/MSS tumors, for whom there are no currently approved frontline immunotherapy-based therapies in the EU.

In the United States, dostarlimab plus chemotherapy followed by dostarlimab monotherapy is FDA approved for the treatment of adult patients with primary advanced or recurrent dMMR/MSI-H endometrial cancer.³ A supplemental biologics license application seeking the expanded indication of dostarlimab plus chemotherapy for the treatment of all adult patients with primary advanced or recurrent endometrial cancer is under priority review.

References

1. Jemperli (dostarlimab) plus chemotherapy application accepted for review by the European Medicines Agency to expand use to all patients with primary advanced or recurrent endometrial cancer. News release. GSK. June 24, 2024. Accessed June 24, 2024. https://www.gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-plus-chemotherapy-application-accepted-for-review-by-ema/
2. Powell MA, Bjørge L, Willmott L, et al. Overall survival in patients with endometrial cancer treated with dostarlimab plus carboplatin-paclitaxel in the randomized ENGOT-EN6/GOG-3031/RUBY Trial. Ann Oncol. Published online June 10, 2024. doi:10.1016/j.annonc.2024.05.546
3. US FDA accepts for priority review GSK’s application for an expanded indication of Jemperli (dostarlimab) plus chemotherapy to include all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. April 24, 2024. Accessed June 24, 2024. https://www.gsk.com/en-gb/media/press-releases/fda-accepts-gsk-application-expanded-indication-of-jemperli-dostarlimab-plus-chemotherapy-include-all-adult-patients-primary-advanced-recurrent-endometrial-cancer/