SHS_492367 ZHAS CMDV 16226

A Phase 2, Open-Label, 2-Arm, Response Rate Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer Who Previously Received Taxane-Based Chemotherapy and Progressed on at Least 1 Novel Hormonal Agent (Enzalutamide and/or Abiraterone Acetate/Prednisone)

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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell, or small cell features.

• Consent to a fresh tumor biopsy before enrollment unless adequate archival tissue is available for molecular analyses.

• DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel.

• 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. Patients with disease spread limited to regional pelvic lymph nodes (below the aortic bifurcation) are not eligible unless bone metastasis is present on bone scan.
Patients may also have metastatic disease documented by bone lesions on whole body radionuclide bone scan.

• Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based regimen for metastatic prostate cancer. Patients may have received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies.

• A history of disease progression during previous treatment for metastatic CRPC with at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) in the opinion of the investigator.

• 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.

Exclusion Criteria:

• Use of systemic 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 (poly ADP ribose polymerase) inhibitor, platinum, cyclophosphamide, or mitoxantrone chemotherapy.

• 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 renal, hepatic, or bone marrow organ dysfunction.

• Known or suspected brain metastasis or active leptomeningeal disease.

• Symptomatic or impending spinal cord compression or cauda equina syndrome.

• Diagnosis of MDS (Myelodysplastic syndromes).

• History of another cancer within 3 years before enrollment with the exception of nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor.

• Gastrointestinal disorder affecting absorption.

• Current or anticipated use of a strong P-gp inhibitor (eg, dronedarone, quinidine, ranolazine, itraconazole, ketoconazole), strong P-gp inducer (eg, rifampin, tipranavir, ritonavir), or strong inhibitor of BCRP (breast cancer resistance protein).
Phase II
Song Zhao, M.D.
Erik Bailey
  • Swedish Medical Center