38MO Progression-free survival (PFS) in primary advanced or recurrent endometrial cancer (pA/rEC) in the overall and mismatch repair proficient (MMR/MSS) populations and in histological and molecular subgroups: Results from part 2 of the RUBY trial

In Part 1 of the phase 3 RUBY trial (NCT03981796) in pA/rEC, patients (pts) receiving dostarlimab (dostar)/carboplatin-paclitaxel (CP) exhibited significant benefits in PFS and overall survival versus CP alone. Outcomes may be further improved by adding a poly(ADP-ribose) polymerase inhibitor (PARPi). Here we report results from Part 2 of RUBY of dostar/CP followed by dostar/niraparib (nira; a PARPi) maintenance therapy in pts with pA/rEC. Pts were randomized 2:1 to dostar 500 mg IV + CP Q3W for 6 cycles followed by dostar 1000 mg IV Q6W + nira (individualized starting dose of 200 or 300 mg) PO daily for ≤3 years from randomization or to placebo (PBO) + CP Q3W for 6 cycles followed by PBOs for ≤3 years. The primary endpoint was PFS in the overall and MMRp/MSS populations. 291 pts were randomized (192 dostar/CP + dostar/nira; 99 PBO/CP). PFS was significantly improved in pts receiving dostar/CP + dostar/nira vs PBO/CP in the overall and MMRp/MSS populations (Table). In pts with endometrioid carcinoma, pts with other histologies, and across most biomarker subgroups (eg, TP53mut), the hazard ratio (HR) directionally favored dostar/CP + dostar/nira in the overall and MMRp/MSS populations. The safety profile observed was consistent with those of the individual agents.Table: 38MOPFSDostar/CP+dostar/niraPBO/CP+PBOHR (95% CI)Overall, n192990.60 (0.43–0.82) P=0.0007Median (95% CI), mo14.5 (11.8–17.4)8.3 (7.6–9.8)-MMRp/MSS, n142740.63 (0.44–0.91) P=0.0060Median (95% CI), mo14.3 (9.7–16.9)8.3 (7.6-9.8)-Pre-specified exploratory analysesNo. of pts with events/No. of ptsAll pts95/19269/99-Endometrioid carcinoma52/11446/670.58 (0.39–0.87)Other histologies42/7623/320.53 (0.32–0.88)Molecular subgroupbPOLεmut0/31/2-adMMR/MSI-H12/3710/170.45 (0.20–1.05)TP53mut27/3910/100.29 (0.13–0.63)No specific molecular profile37/7531/460.61 (0.38–0.99)Not evaluable19/3817/240.71 (0.37–1.37)a<20 events. bBased on whole exome sequencing. Open table in a new tab a<20 events. bBased on whole exome sequencing. RUBY Part 2 met its primary endpoint and is the first study to show significant and clinically meaningful improvement in PFS in the MMRp/MSS and overall populations. The trial is ongoing for OS follow-up. The safety profile observed was generally consistent with the known safety profiles of the individual agents. These data demonstrate a potential role for PARPi maintenance in pts receiving dostar/CP, especially for MMRp/MSS tumors.