An Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

A Phase 2 Efficacy and Safety Study of Niraparib in Men With Metastatic Castration-Resistant Prostate Cancer and DNA-Repair Anomalies

The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of niraparib in men with metastatic castration-resistant prostate cancer (mCRPC) and deoxyribonucleic acid (DNA) repair anomalies.

This is a multicenter and open-label (participants and researchers are aware of the treatment that participants are receiving) study that consists of 4 phases: a Prescreening Phase for biomarker evaluation only, a Screening Phase, a Treatment Phase (Cycle 1 Day 1 and will continue until the study drug is discontinued), a Follow-up Phase (every 3 months after end of treatment visit), and a Long-term Extension Phase (until participants no longer derive benefit from treatment or until further notification on different means of study treatment). Participants will be monitored for safety during the study period, and up to 30 days after the last dose of study drug.

Inclusion Criteria:

• Histologically confirmed prostate cancer (mixed histology is acceptable, with the exception of the small cell pure phenotype, which is excluded)
• Received a taxane-based chemotherapy for the treatment of metastatic prostate cancer with evidence of disease progression on or after treatment, or discontinued from a taxane-based chemotherapy due to an adverse event
• Received a second-generation or later androgen receptor (AR)-targeted therapy (for example, abiraterone acetate plus prednisone, enzalutamide, apalutamide) for the treatment of metastatic prostate cancer with evidence of disease progression or non-metastatic castration-resistant prostate cancer with evidence of subsequent metastasis
• Biomarker-positive by at least one of the following criteria: (a) Biallelic deoxyribonucleic acid (DNA)-repair anomaly based on a sponsor validated blood or tissue assay; (b) Germline pathogenic Breast Cancer gene (BRCA) 1 or BRCA2 by any test (somatic local results must be confirmed as positive by the sponsor-validated assay before dosing)
• Progression of metastatic prostate cancer in the setting of castrate levels of testosterone or history of bilateral orchiectomy at study entry

Exclusion Criteria:

• Prior treatment with a poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor
• Prior platinum-based chemotherapy for the treatment of prostate cancer
• Known history or current diagnosis of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Symptomatic or impending cord compression
• Symptomatic brain metastases