883TiP MOONSTONE/GOG-3032: A phase II, open-label, single-arm study to evaluate the efficacy and safety of niraparib + dostarlimab in patients with platinum-resistant ovarian cancer

Abstract

Niraparib, a poly(ADP-ribose) polymerase inhibitor (PARPi), is approved in the US and Europe for maintenance treatment of patients (pts) with recurrent ovarian (OC), fallopian tube, or primary peritoneal cancer following complete or partial response to platinum-based chemotherapy (chemo), and in the US for the treatment of pts with advanced OC who have been treated with ≥3 prior chemo regimens and whose cancer is BRCA mutated, regardless of platinum sensitivity, or associated with homologous recombination deficiency and platinum sensitivity. Pts with recurrent OC often develop platinum-resistant OC (PROC). In the US, approved treatments for PROC include bevacizumab + chemo. However, despite these therapies, improved outcomes for pts with PROC remain an unmet need. PARPi + anti–programmed death (PD)-1 combinations may have a synergistic antitumor effect. The objective of this currently enrolling study is to evaluate the safety and efficacy of niraparib + dostarlimab (an investigative anti–PD-1 humanized monoclonal antibody) in pts with advanced, relapsed, high-grade PROC without a known BRCA mutation that received and progressed on prior bevacizumab. Eligible pts must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer, received 1−3 lines of prior therapy (one of which included bevacizumab), and have disease progression <6 months from the last administered platinum-based chemo. Those having received a prior PARPi, anti–PD-1, or anti–programmed death-ligand 1 (PD-L1), or with a known or suspected deleterious BRCA mutation, are ineligible. Approximately 150 pts will be enrolled in the US and receive dostarlimab 500 mg IV Q3W for the first 4 doses and then 1000 mg IV Q6W for up to 3 years or until disease progression or toxicity. Pts with baseline bodyweight <77 kg or platelet count <150,000/μL will receive a 200-mg QD starting dose of niraparib, all other pts will receive a 300-mg QD starting dose. The primary endpoint is investigator-assessed objective response rate per RECIST v1.1 in the overall population and PD-L1+ subsets. NCT03955471. Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Hasan Jamal, MSc of GlaxoSmithKline, was provided by Eric Scocchera, PhD and Anne Cooper, MA of Ashfield Healthcare Communications (Middletown, CT, USA). GlaxoSmithKline, Waltham, MA, USA.