Histologically or cytologically confirmed adenocarcinoma of the prostate.
Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (CRPC)
(score on BPI-SF Question #3 must be
For enrollment into Part 2 only (optional in Part 1): Consent to a fresh tumor biopsy
before enrollment unless sufficient archival tissue (preferably of metastatic disease) is
available for molecular analyses
For patients enrolling in Part 2, DNA damage repair deficiency as assessed centrally by an
NGS biomarker mutation panel that contains DDR genes likely to sensitize to PARP
Consent to a saliva sample collection for a germline comparator unless prohibited by local
regulations or ethics committee decision (optional for patients in Part 1).
Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at
Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist
or antagonist for patients who have not undergone bilateral orchiectomy
Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI
Progressive disease at study entry in the setting of medical or surgical castration as
defined by 1 or more of the following 3 criteria:
- Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA
values from 3 assessments with an interval of at least 7 days between assessments.
- Soft tissue disease progression as defined by RECIST 1.1.
- Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or
more new metastatic bone lesions on a whole body radionuclide bone scan.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Life expectancy ≥ 12 months as assessed by the investigator.
Progression of metastatic CRPC while on prior treatment with taxane-based chemotherapy, or
NHT initiated after onset of castration resistance. Men previously treated with NHT or
taxane-based chemotherapy in the hormone sensitive prostate cancer setting or for
nonmetastatic CRPC may be considered.
Treatment with cytotoxic chemotherapy, other hormonal therapy (e.g., bicalutamide,
nilutamide, flutamide, estrogens, 5-alpha reductase inhibitors), biologic therapy including
sipuleucel-T (other than approved bone-targeting agents and GnRH agonist/antagonist
therapy), or radionuclide therapy in the 28 days prior to screening.
Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug
(whichever is longer) before Day 1.
Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate
Prior progression on platinum-based therapy or prior treatment with platinum-based therapy
within the past 6 months
Prior treatment with opioids for pain related to either primary prostate cancer or
metastasis within 28 days before screening unless no pain related to prostate cancer is
reported within 28 days prior to screening.
For patients the investigator chooses to receive enzalutamide, unwilling to agree to avoid
the use of strong cytochrome P450 2C8 (CYP2C8) inhibitors, strong CYP3A4 inducers, or
substrates of CYP3A4, CYP2C9, or CYP2C19 with a narrow therapeutic index.
For patients the investigator chooses to receive abiraterone acetate/prednisone, unwilling
to agree to avoid the use of strong CYP3A4 inducers and CYP2D6 substrates with a narrow
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 (eg, elacridar [GF120918]).
Clinically significant cardiovascular disease
Significant renal dysfunction as defined by any of the following laboratory abnormalities:
? Renal: eGFR
Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30 59 mL/min/1.73 m2) at
Significant hepatic dysfunction as defined by any of the following laboratory abnormalities
on screening labs:
- Total serum bilirubin > 1.5 times the upper limit of normal (ULN) (> 3 × ULN for
patients with documented Gilbert syndrome or for whom indirect bilirubin
concentrations suggest an extrahepatic source of elevation).
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times ULN (>
5 × ULN if liver function abnormalities are due to hepatic involvement).
Absolute neutrophil count
not have received growth factors or blood transfusions within 14 days before obtaining the
hematology values at screening).