MOONSTONE/GOG-3032: Interim analysis of a phase 2 study of niraparib + dostarlimab in patients (pts) with platinum-resistant ovarian cancer (PROC).

5573 Background: PROC is poorly responsive to anticancer therapy. PARP inhibitors such as niraparib may increase neoantigen load and synergize with anti-PD-1 agents. TOPACIO reported a preliminary objective response rate (ORR: 18%) and disease control rate (DCR: 65%) to niraparib + pembrolizumab in pts with OC of any BRCA status. MOONSTONE sought to determine efficacy in pts without BRCA mutation ( BRCAm). Methods: In this phase 2 open-label, single-arm study, eligible pts received 1–3 prior lines of therapy including platinum, taxane, and bevacizumab, had RECIST v1.1 radiographic progression within 6 mo of last platinum line and had no known germline BRCAm. Pts were treated with niraparib 300/200 mg PO daily (based on weight/platelets) and 500 mg dostarlimab IV Q3W (cycles 1–4) followed by 1000 mg Q6W until disease progression, toxicity or consent withdrawal. Programmed death-ligand 1 (PD-L1) positive status was determined by Ventana SP263 assay using visually-estimated combined positive score ≥5%. The primary endpoint was investigator-assessed ORR per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), DCR, and safety. Futility was prespecified as ≤5 responses in the first 40 pts. Results: At interim analysis (data cutoff Oct 6, 2021), 41 pts were enrolled; median age was 65.0 y (range 35–77). At baseline, 8 (20%)/22 (54%)/11 (27%) pts had received 1/2/3 prior lines of therapy, respectively; 26 (63%) pts had primary resistance to platinum therapy and 15 (37%) were sensitive to first platinum treatment. Overall, tumors were PD-L1+/PD-L1–/unknown in 13 (32%)/25 (61%)/3 (7%), respectively. Efficacy results are shown in the Table. Treatment-related adverse events were reported in 95% of pts, most commonly nausea (56%), fatigue (34%), vomiting (32%), and anemia (29%). Conclusions: PROC remains difficult to treat; the ORR observed with niraparib + dostarlimab did not reach the threshold for 2nd-stage accrual in this cohort of pts with PROC, no known BRCAm, and prior bevacizumab treatment. PD-L1 status did not predict response; HRD testing is in process. Although DCR was 29%, futility was declared based on low ORR. The safety of the combination was similar to the safety profile of each monotherapy. Clinical trial information: NCT03955471. [Table: see text]