Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell
or signet cell features
Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC)
(score on BPI-SF Question #3 must be
For enrollment into Part 2 only (optional in Part 1): DDR gene alterations (DDR+) likely to
sensitize to PARP inhibition as determined by prospective analysis (de novo or archival
tissue), or historical analysis (with Sponsor pre-approval)
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
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 consecutive assessments with an interval of at least 7 days between
- 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.
Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before Day 1
(Part 1) or randomization (Part 2) for patients receiving these therapies Eastern
Cooperative Oncology Group (ECOG) performance status ≤ 1.
Eastern Cooperative Oncology Group (ECOG) performance status 1.
Life expectancy ≥ 12 months as assessed by the investigator.
Able to swallow the study drug and have no known intolerance to study drugs or excipients.
Must agree to use a condom when having sex with a pregnant woman from the time of the first
dose of study drug through 120 days after last dose of study drug. Must also agree to use
an additional highly effective form of contraception (Section 4.4.1) from the time of the
first dose of study drug through 120 days 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 120 days after the last
dose of study drug.
Evidence of a personally signed and dated informed consent document (and molecular
prescreening consent if appropriate) indicating that the patient [or a legally acceptable
representative/legal guardian] has been informed of all pertinent aspects of the study.
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures
Any prior systemic cancer treatment initiated in the mCRPC disease state.
Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate
Prior treatment with platinum-based chemotherapy within 6 months prior to Day 1 (Part 1) or
randomization (Part 2), or any history of disease progression on platinum-based therapy at
any time in the past.
Treatment with cytotoxic chemotherapy, other hormonal therapy (eg, 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 Day 1 (Part 1) or randomization
Treatment with any investigational agent within 4 weeks or 5 half-lives of the drug
(whichever is longer) before Day 1 (Part 1) or randomization (Part 2).
Prior treatment with opioids for pain related to either primary prostate cancer or
metastasis within 28 days prior to Day 1 (Part 1) or randomization (Part 2) unless no pain
related to prostate cancer has been reported in the 28 days prior to Day 1 (Part 1) or
randomization (Part 2).
Current or anticipated use of:
1. Medications with potential drug-drug interaction (DDI) with talazoparib: P-gp
inhibitors, P-gp inducers or BCRP inhibitors
2. Medications with potential DDI with enzalutamide: strong cytochrome P450 2C8 (CYP2C8)
inducers, strong CYP3A4 inducers, moderate CYP3A4 inducers and substrates of CYP3A4,
CYP2C9, or CYP2C19 with a narrow therapeutic index.
Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or
randomization (Part 2).
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 metastasis).
Absolute neutrophil count
not have received growth factors or blood transfusions within 14 days before obtaining the
hematology values at screening).
Known or suspected brain metastasis or active leptomeningeal disease.
Symptomatic or impending spinal cord compression or cauda equina syndrome.
History of another cancer including myelodysplastic syndrome or acute myeloid leukemia
within 3 years before Day 1 (Part 1) or randomization (Part 2), with the exception of
uncomplicated 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.
Fertile male subjects who are unwilling or unable to use highly effective methods of
contraception as outlined in this protocol for the duration of the study and for 120 days
after the last dose of investigational product.
Investigator site staff members directly involved in the conduct of the study and their
family members, site staff members otherwise supervised by the investigator, or patients
who are Pfizer employees, including their family members, directly involved in the conduct
of the study.
Other acute or chronic medical (concurrent disease, infection, or comorbidity) or
psychiatric condition including recent (within the past year) or active suicidal ideation
or behavior or laboratory abnormality that interferes with ability to participate in the
study, may increase the risk associated with study participation or investigational product
administration, or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this