Background: Despite surgery and CT (paclitaxel + carboplatin ± bevacizumab [bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3 or 4 OC. Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that has recently demonstrated efficacy in 1L therapy. Dostarlimab (TSR-042) is an anti-programmed death (PD)-1 humanized monoclonal antibody that has shown clinical activity as monotherapy in early phase trials. The currently enrolling ENGOT-OV44/FIRST study will compare efficacy and safety of CT + dostarlimab + niraparib ± bev (Arm 3) vs CT + niraparib ± bev (Arm 2). Methods: Eligible pts are ≥18 years of age, with FIGO stage 3 or 4 non-mucinous epithelial OC, ECOG performance status < 2, and tumor tissue available for PD-1 ligand (PD-L1) testing. After cycle 1 of CT, pts are stratified by concurrent bev use, BRCA mutation/homologous recombination repair status, and disease burden, then randomized 1:2 into trial Arms 2 and 3 (Table). Dostarlimab is administered at 500 mg IV Q3W during the CT period, then 1000 mg IV Q6W during the maintenance period. Niraparib dosing is 200 mg PO QD for pts with baseline bodyweight (BW) < 77 kg and/or platelet count (PC) < 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. The dual primary endpoints are PFS, based on investigator assessment per RECIST v1.1, in both PD-L1+ and all patients. Initially the study enrolled pts to Arm 1. This arm was discontinued following positive results from the PRIMA/ENGOT-OV26/GOG-3012 and PAOLA-1/ENGOT-OV25 studies. This allows investigators to offer the current standard of care to all patients. Clinical trial information: NCT03602859, EUDRACT 2018-000413-20

*Bev is optional in all arms.