A phase III randomized, placebo-controlled, double-blind study of niraparib plus abiraterone acetate and prednisone versus abiraterone acetate and prednisone in patients with metastatic prostate cancer (NCT03748641).

Abstract

TPS257 Background: Preclinical data suggest synergistic antitumor activity when the PARP inhibitor (PARPi) niraparib is combined with the androgen pathway inhibitor abiraterone acetate. (1) The addition of a PARPi to abiraterone acetate plus prednisone (AAP) showed improved radiographic progression-free survival (rPFS) vs AAP alone in patients with mCRPC regardless of DNA repair gene defect (DRD) status. (2) Interim results from a phase 1 study support safety and tolerability of niraparib 200 mg combined with AAP in patients with mCRPC. (3) The objective of this Phase 3 study is to compare the efficacy and safety of niraparib plus AAP versus AAP with placebo as first-line therapy for mCRPC. Methods: This ongoing multicenter MAGNITUDE study will open in 300 sites across 28 countries and will enroll patients with mCRPC who have not received treatment in the metastatic castrate resistant setting other than ongoing androgen deprivation therapy [ADT] and ≤4 months of AAP. The DRD positive cohort (Cohort 1, n=400) will comprise patients whose tumors have DRD, as determined by a previously validated plasma or tissue assay. The cohort without DRD (Cohort 2, n=600) will enroll patients whose tumors are not found to have DRD. Enrollment began in February 2019. The primary objective of the study is to compare radiographic progression-free survival (rPFS) as assessed by blinded independent central radiology review for patients treated with niraparib and AAP versus placebo and AAP. To test superiority of the combination vs AAP, sample sizes were estimated to provide 92% power to detect HR≤0.65 rPFS in the DRD positive cohort and 94% power to detect HR≤0.67 in rPFS in the cohort without DRD, both at a 2-tailed level of significance of 0.05. The main secondary objectives are time to symptomatic progression, time to cytotoxic chemotherapy, and overall survival. Safety and pharmacokinetic profiles will be evaluated.1) Rajendra N, et al. Cancer Res 2019;79 (13 Suppl): Abstract nr 2134. 2) Clarke N, et al. Lancet Oncol. 2018;(7):975-986. 3) Saad, et al. Ann Oncol, 2018;29 (suppl 8), mdy284.043, https://doi.org/10.1093/annonc/mdy284.043 ). Clinical trial information: NCT03748641.