1. At least 18 years of age.
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without
neuroendocrine differentiation, signet cell, or small cell features.
3. Consent to a fresh tumor biopsy before enrollment unless adequate archival tissue is
available for molecular analyses.
4. DNA damage repair deficiency as assessed centrally by a gene mutation biomarker
panel.
5. Consent to a saliva sample collection for a germline comparator, unless prohibited by
local regulations or ethics committee (EC) decision.
6. Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.
7. Bilateral orchiectomy or ongoing androgen deprivation therapy with a
gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical
castration).
8. 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.
9. 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.
10. 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.
11. 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.
12. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before
day 1 for patients receiving these therapies.
13. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
14. Estimated life expectancy of ≥ 6 months as assessed by the investigator.
1. 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.
2. Prior treatment with a PARP (poly ADP ribose polymerase) inhibitor, platinum,
cyclophosphamide, or mitoxantrone chemotherapy.
3. Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy)
before day 1.
4. Major surgery within 2 weeks before day 1.
5. Clinically significant cardiovascular disease.
6. Significant renal, hepatic, or bone marrow organ dysfunction.
7. Known or suspected brain metastasis or active leptomeningeal disease.
8. Symptomatic or impending spinal cord compression or cauda equina syndrome.
9. Diagnosis of MDS (Myelodysplastic syndromes).
10. 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.
11. Gastrointestinal disorder affecting absorption.
12. 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).l