A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• At least 18 years of age.
• Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features.
• Patients must have measurable soft tissue disease per RECIST 1.1
• DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel (testing of de novo or archival tumor tissue (via central laboratory) or prior historical testing (with Sponsor approval) using the Foundation Medicine, FoundationOne CDx™ NGS gene panel test.
• Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.
• Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.
• Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).
• Progressive disease at study entry defined as 1 or more of the following 3 criteria:
• A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be ≥ 2 μg/L (2 ng/mL) if qualifying solely by PSA progression.
• Soft tissue disease progression as defined by RECIST 1.1.
• Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan.
• Metastatic disease.
• Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies.
• Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC.
• Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Estimated life expectancy of ≥ 6 months as assessed by the investigator.
• Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements.
• Must use a condom when having sex from the time of the first dose of study drug through 4 months after last dose of study drug. A highly effective form of contraception must be used from the time of the first dose of study drug through 4 months after last dose of study drug when having sex with a non pregnant female partner of childbearing potential.
• Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug.
• Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

• 1. Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day 1.
• Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy <=6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded.
• Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within 4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during study participation
• Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day 1.
• Major surgery within 2 weeks before day 1.
• Clinically significant cardiovascular disease.
• Significant ren