FIRST/ENGOT-OV44: A phase 3 clinical trial of dostarlimab (dost) and niraparib (nira) in first-line (1L) advanced ovarian cancer (aOC).

Abstract

LBA5506 Background: The FIRST/ENGOT-OV44 trial evaluated adding dost, a programmed cell death protein-1 inhibitor, to 1L platinum-based chemotherapy (PBCT) and nira maintenance (MT) ± bevacizumab (bev) in patients (pts) with aOC. Methods: In this randomized, double-blind, phase 3 trial, pts with newly diagnosed stage III–IV, high-grade nonmucinous epithelial OC received 1-cycle run-in of PBCT ± bev and were randomized (1:1:2) to arm 1 (PBCT+placebo [PBO] with PBO MT), arm 2 (PBCT+PBO with nira+PBO MT), or arm 3 (PBCT+dost with dost+nira MT). Stratification factors included intended bev use (yes/no), homologous recombination repair (HRR) mutation status ( BRCA -mutated; BRCA wild-type HRR-positive; BRCA wild-type HRR-negative/not determined), and stage III disease with postoperative residual disease <1 cm (yes/no). After approvals for 1L MT poly(ADP-ribose) polymerase inhibitors, arm 1 enrollment closed, and pts were randomized (1:2) to arms 2 or 3. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST v1.1, assessed in arms 2 and 3, and analyzed per randomized treatment. Safety was assessed among pts who received ≥1 dose of study treatment and analyzed per treatment received. The data cutoff was October 31, 2024. Results: Randomization was from 14Nov2018 to 05Jan2021. Efficacy analyses included 1138 randomized pts (arm 2, n=385; arm 3, n=753; stage IV disease at diagnosis, 37.3%; planned interval surgery, 54.6%; inoperable, 9.8%; homologous recombination-deficient [HRd] disease, 39.0%; programmed cell death ligand 1 [PD-L1]–positive tumors, 33.4% [of n=951 with nonmissing PD-L1 status]; median follow-up, 45.9 mo [IQR, 24.2–54.1]). Patient characteristics were balanced between arms. PFS was statistically significantly longer in arm 3 vs arm 2 (median PFS, 20.63 vs 19.19 mo, respectively; hazard ratio [HR], 0.85; 95% CI, 0.73–0.99; P =0.0351). PFS was reported in subgroups with PD-L1–positive tumors (HR, 0.84; 95% CI, 0.61–1.17), HRd tumors (HR, 0.95; 95% CI, 0.72–1.24), and concurrent bev use (yes: HR, 0.84; 95% CI, 0.68–1.03; no: HR, 0.86; 95% CI, 0.69–1.08).There was no statistically significant difference in overall survival (OS), a key secondary endpoint, between arms 3 and 2 (median OS, 44.39 vs 45.37 mo, respectively; HR, 1.01; 95% CI, 0.86–1.19; P =0.9060). The safety population (N=1321; arms 1–3) included 34 pts randomized to arm 1 who, upon unblinding, received arm 2 treatment; 10 randomized pts did not receive study treatment and were excluded from safety analyses. Median duration of exposure was 11.3, 15.2, and 15.2 mo in arms 1, 2, and 3, respectively. Safety results were generally consistent with the known profiles of each agent of the study. Conclusion: Adding dost to 1L PBCT and nira MT ± bev improved PFS in pts with aOC. No OS difference was observed. Clinical trial information: NCT03602859 .