QUADRA: A phase 2, open-label, single-arm study to evaluate niraparib in patients (pts) with relapsed ovarian cancer (ROC) who have received ≥3 prior chemotherapy regimens.

5514 Background: PARP inhibitors (PARPi) are approved as active treatment only for pts with BRCA mutations. The PARPi niraparib demonstrated increased PFS vs placebo in the maintenance setting of platinum (plat) responsive ROC. Niraparib was effective regardless of BRCAmut or homologous recombination deficiency (HRD) status, but an increased treatment effect was observed in the HRDpos population. QUADRA (NCT02354586) evaluated niraparib active treatment in ROC pts. Based on the results of NOVA, the primary objective in QUADRA was to determine ORR in plat sensitive, HRDpos patients. Methods: Eligible pts had grade 2 or 3 serous ROC, ≥3 prior lines of chemo and measurable disease. Pts were evaluated for BRCAmut and HRD status (MyChoice HRD Test). HRDpos included germline or tumor BRCA mutation or an HRD score ≥42. Pts received niraparib 300 mg once daily until progression; treatment emergent adverse events (TEAEs) were managed with dose reduction to 200 or 100 mg. The primary endpoint was ORR per RECIST v1.1. Results: 463 pts were treated. Median age was 65 (range: 29-91). 162 pts were plat refractory; 152 plat resistant; 118 plat sensitive; 31 unknown. In HRDpos, plat sensitive pts who had received ≥3 regimens (median: 3 [range: 3-9]), without prior PARPi (N = 51) ORR was 27.5% (95% CI: 15.9%, 41.7%); DCR was 68.6%; DOR was 9.2 mos. Of the 51 pts, ORR was 38.9% (7/18) in BRCAmut and 21.2% in BRCAwt pts (7/33). 260 (56.2%) pts had grade ≥3 treatment-related TEAEs. The most common grade ≥3 TEAEs were thrombocytopenia (27.9%), anemia (24.9%), and neutropenia (12.4%). Grade ≥3 thrombocytopenia was 27.5% at 300 mg, 4.7% at 200 mg, and 2.7% at 100 mg. Hematologic TEAEs were most frequent in the first month and decreased in frequency and severity after dose reduction during months 2-3. Conclusions: Niraparib demonstrated durable anti-cancer activity in this heavily treated, HRDpos ROC population (4th line or greater), including BRCAwt pts. Toxicities, consistent with previous niraparib studies, were manageable with dose reduction and generally resolved within 3 mos. Final data including ORR in the total population (N = 463) and results in other subgroups will be presented. Disclosure Funded by TESARO, Inc. Clinical trial information: NCT02354586.

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