An open-label phase II study of dostarlimab (TSR-042), bevacizumab (bev), and niraparib combination in patients (pts) with platinum-resistant ovarian cancer (PROC): cohort A of the OPAL trial

Abstract

Objectives: Preclinical evidence suggests that PARP inhibition (PARPi), anti-PD-1 therapy, and anti-angiogenic therapies have interactions that may support synergistic antitumor activity in pts with PROC. This phase 2 study evaluated activity of combination therapy with the PARPi niraparib, the PD-1 inhibitor dostarlimab, and bev in pts with PROC. Methods: Eligible pts had high-grade, platinum-resistant (progressed ≤6 mo after completion of ≥4 cycles of platinum-based chemo), recurrent epithelial ovarian, fallopian tube, primary peritoneal cancer, or recurrent carcinosarcoma of the ovary (high-grade mixed histology permitted). Pts had 1–2 prior lines of anticancer therapy for OC, and no prior therapy with an anti-PD-1/-L1 or PARPi. Pts received a regimen of 500 mg dostarlimab Q3W x 4, then 1000 mg Q6W + 15 mg/kg bev Q3W + niraparib 300 mg or 200 mg (for weight <77 kg or platelet count <150,000/µL at screening) QD until discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary objectives were progression-free survival (PFS), safety, and disease control rate (DCR). A posthoc analysis by biomarker (BRCA mutation [BRCAm] status, homologous recombination repair mutation [HRRm], and combined positive score [CPS; a measure of intratumoral and immune infiltrate PD-L1 expression], prior lines of therapy, and prior bev use) was performed. Results: Conclusions: Conclusion: Triplet therapy with niraparib, dostarlimab, and bev is tolerable and demonstrated clinical activity in pts with PROC, most of which were BRCA or HRR wt. AEs were as expected. Clinical trial identification: NCT03574779. Funding: GlaxoSmithKline. Preclinical evidence suggests that PARP inhibition (PARPi), anti-PD-1 therapy, and anti-angiogenic therapies have interactions that may support synergistic antitumor activity in pts with PROC. This phase 2 study evaluated activity of combination therapy with the PARPi niraparib, the PD-1 inhibitor dostarlimab, and bev in pts with PROC. Eligible pts had high-grade, platinum-resistant (progressed ≤6 mo after completion of ≥4 cycles of platinum-based chemo), recurrent epithelial ovarian, fallopian tube, primary peritoneal cancer, or recurrent carcinosarcoma of the ovary (high-grade mixed histology permitted). Pts had 1–2 prior lines of anticancer therapy for OC, and no prior therapy with an anti-PD-1/-L1 or PARPi. Pts received a regimen of 500 mg dostarlimab Q3W x 4, then 1000 mg Q6W + 15 mg/kg bev Q3W + niraparib 300 mg or 200 mg (for weight <77 kg or platelet count <150,000/µL at screening) QD until discontinuation. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary objectives were progression-free survival (PFS), safety, and disease control rate (DCR). A posthoc analysis by biomarker (BRCA mutation [BRCAm] status, homologous recombination repair mutation [HRRm], and combined positive score [CPS; a measure of intratumoral and immune infiltrate PD-L1 expression], prior lines of therapy, and prior bev use) was performed. Conclusion: Triplet therapy with niraparib, dostarlimab, and bev is tolerable and demonstrated clinical activity in pts with PROC, most of which were BRCA or HRR wt. AEs were as expected.