Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC

  • End date
    Nov 25, 2024
  • participants needed
  • sponsor
Updated on 23 September 2021


This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.


Part 1 is an open-label, non-randomized, safety and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK at select sites. Part 2 is a randomized, double-blind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide in patients with mCRPC.

Condition mCRPC, DDR+ mCRPC, DDR+ mCRPC, mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR), mCRPC With DNA Damage Repair Deficiencies (DDR)
Treatment Talazoparib with NHT, Placebo with NHT, Talazoparib with enzalutamide, Placebo with enzalutamide
Clinical Study IdentifierNCT03395197
Last Modified on23 September 2021


Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate
withoutsmall cell or signet cell features
Asymptomatic or mildly symptomatic metastatic castration resistant prostate
cancer (mCRPC) (score on BPI-SF Question #3 must be < 4)
For enrollment into Part 2 only (optional in Part 1): assessment of DDR
mutation status
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 screening
Metastatic disease in bone documented on bone scan or in soft tissue
documented on CT/MRI scan
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 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
Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or
randomization (Part 2) is allowed but not mandatory
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
Must agree to use a condom when having sex with a partner from the time of the
first dose of study drug through 4 months after last dose of study treatment
Must also agree for female partner of childbearing potential to use an
additional highly effective form of contraception from the time of the first
dose of study treatment through 4 months after last dose of study treatment
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
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

Exclusion Criteria

Any prior systemic cancer treatment initiated in in the non metastatic CRPC
and mCRPC disease state
Patients whose only evidence of metastasis is adenopathy below the aortic
Prior treatment with second-generation androgen receptor inhibitors
(enzalutamide, apalutamide, and darolutamide), a PARP inhibitor
cyclophosphamide, or mitoxantrone for prostate cancer
Prior treatment with platinum-based chemotherapy within 6 months (from the
last dose) prior to Day 1 (Part 1) or randomization (Part 2), or any history
of disease progression on platinum-based therapy within 6 months (from the
last dose)
Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel
T, or radionuclide therapy received in the castration-sensitive prostate
cancer is NOT exclusionary if discontinued in the 28 days prior to Day 1 (Part
) or randomization (Part 2)
Treatment with any investigational agent within 4 weeks 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)
Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or
randomization (Part 2)
Major surgery (as defined by the investigator) within 2 weeks before Day 1
(Part 1) or randomization (Part 2), or palliative localized radiation therapy
within 3 weeks before randomization (Part 2)
Clinically significant cardiovascular disease
Significant renal dysfunction as defined by any of the following laboratory
Renal: eGFR < 30 mL/min/1.73 m2 by the MDRD equation (available via
Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59
mL/min/1.73 m2) at screening
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)
Albumin <2.8 g/dL
Absolute neutrophil count < 1500/L, platelets < 100,000/L, or hemoglobin < 9
g/dL (may 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
Any history of myelodysplastic syndrome, acute myeloid leukemia, or prior
malignancy except any of the following
Carcinoma in situ or non melanoma skin cancer
Any prior malignancies 3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage
Stage 0 or Stage 1 cancer <3 years before randomization that has a remote probability of recurrence or progression in the opinion of the investigator
Gastrointestinal disorder affecting absorption
Fertile male subjects who are unwilling or unable to use highly effective
methods of contraception for the duration of the study and for 4 months 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 study
History of seizure or any condition that may predispose to seizure (eg, prior
cortical stroke, significant brain trauma). Also, history of loss of
consciousness or transient ischemic attack within 12 months of randomization
(Part 2)
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note