VP2-2023: Dostarlimab+chemotherapy for the treatment of primary advanced or recurrent (A/R) endometrial cancer (EC): A placebo (PBO)-controlled randomised phase III trial (ENGOT-EN6-NSGO/GOG-3031/RUBY)

Carboplatin-paclitaxel (CP) is standard of care (SOC) for first-line treatment primary A/R EC; median OS <3 yrs. Use anti–PD-1s with chemo has improved outcomes in multiple tumour types. RUBY (NCT03981796) evaluated the efficacy and safety anti–PD-1 dostarlimab (D)+CP EC compared CP alone. a phase III, global, randomised, double-blind, multicentre, PBO-controlled study. Pts advanced stage III or IV first recurrent were randomised 1:1 to receive 500 mg, PBO, plus carboplatin AUC 5 paclitaxel 175 mg/m2Q3W (6 cycles), followed by 1000 monotherapy Q6W up 3 Primary endpoints PFS investigator assessment per RECIST v1.1 OS. Graphical method was used hypothesis testing dMMR/MSI-H population, then overall population. A prespecified exploratory analysis MMR proficient (MMRp)/MS stable (MSS) pts also performed. Safety assessed. Of 494 (245 D+CP; 249 PBO+CP), 23.9% had tumours (53 65 47.8% disease; 18.6% 33.6% disease, respectively. results are presented table. Discontinuation PBO due TEAE occurred 17.4% receiving D+CP 9.3% PBO+CP. The profile generally consistent each drug.TableVP2-2023HR (95% CI) P% Probability at 24 mo CI)PFSdMMR/MSI-H D+CP0.28 (0.162–0.495)<0.000161.4 (46.3–73.4) PBO+CP15.7 (7.2–27.0)Overall D+CP0.64 (0.507–0.800)<0.000136.1 (29.3–42.9) PBO+CP18.1 (13.0–23.9)MMRp/MSSaNo MMRp/MSS planned. Maturity: D+CP0.76 (0.592–0.981) NA28.4 (21.2–36.0) PBO+CP18.8 (12.8–25.7)OSOverallb≈33%. (0.464–0.870)0.0021eP-value ≤0.00177 required statistical significance this analysis.71.3 (64.5–77.1) PBO+CP56.0 (48.9–62.5)dMMR/MSI-Hc≈26%. D+CP0.30 (0.127–0.699) NA83.3 (66.8–92.0) PBO+CP58.7 (43.4–71.2)MMRp/MSSd≈36%. D+CP0.73 (0.515–1.024) NA67.7 (59.8–74.4) PBO+CP55.1 (46.8–62.5)a No Maturity:b ≈33%.c ≈26%.d ≈36%.e P-value analysis. Open table new tab showed statistically significant clinically meaningful benefits populations vs relevant benefit observed An early trend toward all populations. combination dostarlimab+CP represents SOC newly diagnosed EC.