Abstract
Background: Part 1 of the RUBY trial (NCT03981796) evaluated dostarlimab plus carboplatin-paclitaxel- paclitaxel compared with placebo plus carboplatin-paclitaxel- paclitaxel in patients with primary advanced or recurrent endometrial cancer (EC). At the fi rst interim analysis, the trial met one of its dual primary endpoints with statistically significant fi cant progression-free survival benefits fi ts in the mismatch repair-deficient/microsatellite fi cient/microsatellite instability-high (dMMR/MSI-H) and overall populations. Overall survival (OS) results are reported from the second interim analysis. Patients and methods: RUBY is a phase III, global, double-blind, randomized, placebo-controlled trial. Part 1 of RUBY enrolled eligible patients with primary advanced stage III or IV or fi rst recurrent EC who were randomly assigned (1 : 1) to receive either dostarlimab (500 mg) or placebo, plus carboplatin-paclitaxel- paclitaxel every 3 weeks for 6 cycles followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. OS was a dual primary endpoint. Results: A total of 494 patients were randomized (245 in the dostarlimab arm; 249 in the placebo arm). In the overall population, with 51% maturity, RUBY met the dual primary endpoint for OS at this second interim analysis, with a statistically significant fi cant reduction in the risk of death [hazard ratio (HR) = 0.69, 95% confidence fi dence interval (CI) 0.540.89, P = 0.0020] in patients treated with dostarlimab plus carboplatin-paclitaxel- paclitaxel versus carboplatin-paclitaxel- paclitaxel alone. The risk of death was lower in the dMMR/MSI-H population (HR = 0.32, 95% CI 0.17-0.63, nominal P = 0.0002) and a trend in favor of dostarlimab was seen in the mismatch repair-proficient/microsatellite fi cient/microsatellite stable population (HR = 0.79, 95% CI 0.60-1.04, nominal P = 0.0493). The safety profile fi le for dostarlimab plus carboplatin- paclitaxel was consistent with the fi rst interim analysis. Conclusions: Dostarlimab in combination with carboplatin-paclitaxel- paclitaxel demonstrated a statistically significant fi cant and clinically meaningful OS benefit fi t in the overall population of patients with primary advanced or recurrent EC while demonstrating an acceptable safety profile. fi le.