Background: Niraparib improves progression-free survival (PFS) in pts with newly diagnosed AOC after complete or partial response to first-line, platinum-based chemotherapy. In the PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) trial, pts were treated with a fixed starting dose (FSD) of 300 mg QD until a protocol amendment introduced the individualized starting dose (ISD) regimen: 200 mg QD for pts with baseline bodyweight (BW) < 77 kg and/or platelet count (PC) < 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. Here, we developed a population pharmacokinetic (PopPK) model for niraparib and evaluated exposure-response relationships for pts receiving niraparib using safety and efficacy data from PRIMA. Methods: The PopPK model for niraparib was developed based on 7418 plasma samples from 1442 pts from 4 studies: PN001, NOVA, QUADRA, and PRIMA. PRIMA PK samples were collected on cycle 1, day 1 (C1D1), C2D1 pre-dose and 2 h post-dose, C4D1, and C8D1 pre-dose (or EOT if patient discontinued before C8D1). The relationship between PopPK model-based prospective exposure (average concentration [C_ave] until progression/death) and efficacy (PFS) were evaluated in pts receiving niraparib in both the homologous-recombination deficient (HRd) and overall population. The relationship between model-predicted exposure metrics and incidence of clinically relevant adverse events (AEs) was analyzed using univariate logistic regression in pts receiving niraparib. Results: Of 484 pts receiving niraparib in PRIMA, 480 had PK data and were included in the efficacy and safety analysis. The safety exposure-response showed significant associations (p≤0.0128) between increasing niraparib exposure and increasing probability of experiencing any-grade and grade ≥3 AEs, except grade ≥3 hypertension. The incidence of AEs, including thrombocytopenia, was lower in pts who received a 200-mg ISD. Efficacy was not compromised in these pts. Conclusions: Niraparib exposure was associated with increased risk of select AEs. However, the ISD regimen decreased AE risk without compromising efficacy. Clinical trial information: NCT02655016