Inclusion Criteria:

• Male ≥ 18 years of age at the time the informed consent form is signed.
• Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (pure small-cell histologies or pure high-grade neuroendocrine histologies are excluded; neuroendocrine differentiation is allowed) that is metastatic.
• Surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM). If currently being treated with luteinizing hormone–releasing hormone (LHRH) analogs (patients who have not undergone an orchiectomy), therapy must be continued throughout the study.
• Eligible for treatment with physician’s choice of comparator treatment, selected prior to randomization, per the corresponding prescribing information.
• Evidence of disease progression after treatment with one prior next-generation AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide, or investigational AR-targeted agent); treatment with the older anti-androgen therapies such as bicalutamide, flutamide, and nilutamide are not counted toward this limit.
• Disease progression after initiation of most recent therapy is based on any of the following criteria:
  • Rise in PSA: a minimum of two consecutive rising levels, with an interval of ≥ 1 week between each determination. The most recent screening measurement must have been ≥ 2 ng/mL;
  • Transaxial imaging: new or progressive soft tissue masses on CT or MRI scans as defined by modified RECIST Version 1.1;
  • Radionuclide bone scan: at least two new metastatic lesions.
• All patients must have a deleterious gene mutation in BRCA1/2 or ATM. Mutations may be identified by local testing or through central testing by the sponsor of plasma or tumor tissue.
• For local test results, the classification of the mutation as deleterious must be documented in the patient’s medical record.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Have adequate organ function confirmed by the following clinical laboratory values obtained within 14 days prior to the first dose of study drug:
  • Bone Marrow Function i. ANC ≥ 1.5 × 109/L:
    • Platelets > 100 × 109/L;
    • Hemoglobin ≥ 10 g/dL independent of transfusion within 14 days.
  • Hepatic Function:
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × the upper limit of normal (ULN);
    • Bilirubin ≤ 1.5 × ULN (< 2 x ULN if hyperbilirubinemia is due to Gilbert’s syndrome).
  • c. Renal Function:
    • Estimated glomerular filtration rate (GFR) ≥ 45 mL/min using the Cockcroft-Gault formula.
• Male patients who are committed to undertaking the following measures for the duration of the study and after the last dose of study drug for the time period specified:
  • Use a condom during sex while being treated and for 3 months after the last dose of study drug;
  • Do not make semen donations during treatment and for 3 months after the last dose of rucaparib;
  • Those with female partners of childbearing potential may be enrolled if they are:
    • Documented to be surgically sterile (ie, vasectomy);
    • Committed to practicing true abstinence during treatment and for 3 months after the last dose of study drug; or
    • Committed to using a highly effective method of contraception (refer to Section 6.5) with their partner during treatment and for 3 months following the last dose of study drug.
• Have a life expectancy of at least 6 months.

Exclusion Criteria:

• Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer:
  • Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to enroll in the study provided all therapy was completed > 6 months prior and/or bone marrow transplant (BMT) > 2 years prior to first dose of rucaparib.
• Prior treatment with any PARPi.
• Prior treatment with chemotherapy (eg docetaxel, mitoxantrone, cyclophosphamide, platinum-based agents) for mCRPC. Prior treatment with docetaxel (or other taxane chemotherapy) administered for castration-sensitive disease is permitted .
• Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable (not requiring steroids for at least 4 weeks prior to first dose of study drug) and have appropriate scans at screening assessment.
• Symptomatic or impending spinal cord compression unless appropriately treated, clinically stable, and asymptomatic.
• Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study drug.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or history of chronic hepatitis B or C, with the exception of patients with sustained virologic response after completion of treatment for hepatitis C.
• Received treatment with chemotherapy, antibody therapy, immunotherapy, gene therapy, angiogenesis inhibitors, or experimental drugs within < 14 days prior to first dose of study drug. Treatment with hormonal therapies (with the exception of LHRH analog) must be discontinued at least 7 days prior to the first dose of study drug.
• Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor.
• Initiated low-dose corticosteroid, bisphosphonate, or denosumab therapy or adjusted low-dose corticosteroid, bisphosphonate, or denosumab dose/regimen within < 28 days prior to first dose of study drug. Patients on a stable low-dose corticosteroid, bisphosphonate, or denosumab regimen are eligible and may continue treatment.
• Non-study related minor surgical procedure within < 5 days, or major surgical procedure within < 21 days, prior to first dose of study drug; in all cases, the patient must be sufficiently recovered and stable before treatment administration.
• Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.