A Study of Talazoparib With or Without Enzalutamide in People With Prostate Cancer Who Have Previously Received Abiraterone Acetate

NCT06844383 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: c24-349
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out whether talazoparib in combination with enzalutamide or talazoparib alone delays cancer progression in people with metastatic castration-resistant prostate cancer (mCRPC) who have homologous recombination repair (HRR) mutations and have previously received abiraterone acetate.

Conditions

Prostate Cancer (Adenocarcinoma); mCRPC (Metastatic Castration-resistant Prostate Cancer)

Keywords

talazoparib; enzalutamide; PARP inhibitor; TALENT; androgen receptor signaling inhibitor (ARSI); Prostate Cancer Clinical Trials Consortium, LLC (PCCTC); c24-349

Outcome Measures

Primary Outcomes (1)

• radiographic progression free survival (rPFS)

  To compare the efficacy of talazoparib + enzalutamide to talazoparib alone as measured by rPFS as assessed by the Investigator.

  From treatment initiation until documented disease progression, death, lost to follow-up, withdrawal, administrative censoring at the time of final analysis, assessed at approximately 42 months from the start of enrollment.

Secondary Outcomes (7)

• Time to PSA50

  Time from treatment initiation until observed PSA50, assessed at approximately 42 months from the start of enrollment.

• Time to PSA Progression

  From treatment initiation until documented PSA progression, assessed at approximately 42 months from the start of enrollment.

• Quality of Life (QoL) by Functional Assessment of Cancer Therapy-Prostate (FACT-P)

  From prior to treatment initiation (screening) until treatment discontinuation, assessed at approximately 42 months from the start of enrollment.

• Quality of Life (QoL) by Functional Assessment of Cancer Intervention Therapy-Fatigue Scale (FACIT-Fatigue)

  From prior to treatment initiation (screening) until treatment discontinuation, assessed at approximately 42 months from the start of enrollment.

• Quality of Life (QoL) by Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog)

  From prior to treatment initiation (screening) until treatment discontinuation, assessed at approximately 42 months from the start of enrollment.

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Talazoparib (0.5 mg PO QD) and enzalutamide (160 mg PO QD) will be administered in continuous 28-day cycles.

Drug: Talazoparib with enzalutamide

Arm B

EXPERIMENTAL

Talazoparib (1 mg PO QD) will be administered in continuous 28-day cycles.

Drug: Talazoparib

Interventions

Talazoparib with enzalutamide DRUG

Talazoparib (0.5 mg PO QD) and enzalutamide (160 mg PO QD) will be administered in continuous 28-day cycles.

Also known as: Talzenna, Xtandi

Arm A

Talazoparib DRUG

Talazoparib (1 mg PO QD) will be administered in continuous 28-day cycles.

Also known as: Talzenna

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
• NOTE: Privacy authorization may be either included in the informed consent or obtained separately.
• Participants ≥ 18 years of age.
• Are willing to be randomized into either study arm and adhere to the study protocol.
• Ability to swallow study capsules and/or tablets whole.
• Are willing to remain on study treatment and to continue undergoing study imaging despite PSA progression unless clinically deteriorating.
• Histological or cytological proof of adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.
• Presence of a pathogenic homologous recombination repair mutation in at least one of the following genes on tumor tissue or circulating tumor DNA testing: BRCA1, BRCA2, ATM (limited to 15% of enrolled participants), CDK12, CHEK2, PALB2, MLH1, NBN, ATR, FANCA, MRE11A, RAD51C. Assessment of HRR mutation status by germline or somatic testing. All testing must be per Clinical Laboratory Improvement Amendments (CLIA)-certified assay and may have occurred at any time prior to or at screening (not required to be completed within the screening window).
• Metastatic castration-resistant prostate cancer (mCRPC) as demonstrated by one of the following:
• Metastatic disease documented by conventional imaging: computed tomography (CT)/magnetic resonance imaging (MRI) chest/abdomen/pelvis and bone scan are required to be performed, but metastases do not need to be seen on both modalities. Measurable disease is not required.
• Unequivocal prostate-specific membrane antigen (PSMA) positron emission tomography (PET) only defined metastatic disease with negative conventional imaging. PSMA PET imaging is not required to be performed, but may be used to document metastases when relevant.
• Received prior abiraterone acetate with prednisone for mHSPC or locally advanced disease and on which progressed via a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination or radiographic progression by any form of imaging.
• Progressive disease at start of treatment and in the setting of medical or surgical castration as defined by 1 or more of the following 4 criteria:
• PSA progression defined as 2 rising PSA levels, above an initial reference value, taken with a minimum of a 1-week interval. If PSA rise is the only indication of progression at start of study treatment, a minimum PSA of 1.0 ng/mL is required and all measured PSA values have to be considered to make a determination of progression.
• Soft tissue disease progression as defined by RECIST 1.1.

You may not qualify if:

• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer or superficial bladder cancer.
• Participants who received chemotherapy for castration-sensitive prostate cancer are still eligible provided chemotherapy was completed \>6 months prior to start of study treatment.
• Use of investigational agents for the treatment of prostate cancer within 4 weeks of start of study treatment.
• Prior treatment with a PARP inhibitor.
• Concurrent treatment with crizotinib.
• Prior platinum-based chemotherapy for the treatment of prostate cancer.
• Current or planned use of potent P-gp inhibitors within 7 days prior to randomization. The P-gp inhibitors include: amiodarone, carvedilol, clarithromycin, cobicistat, dronedarone, erythromycin, glecaprevir/pibrentasvir, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, sofosbuvir/velpatasvir/voxilaprevir, telaprevir, tipranavir, valspodar, and verapamil.
• Current use of strong cytochrome P450 2C8 (CYP2C8) inhibitors (e.g., clopidogrel, gemfibrozil) and inducers (e.g., rifampin), strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine and St. John's Wort), moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil and nafcillin), or substrates of CYP3A4 (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus and tacrolimus), CYP2C9 (e.g., phenytoin, warfarin), or CYP2C19 (e.g., S-mephenytoin) with a narrow therapeutic index unless considered medically necessary to treat a life-threatening condition.
• Participants treated with strong cytochrome P450 2C8 (CYP2C8) inhibitors (e.g., clopidogrel, gemfibrozil) within 7 days from randomization are not eligible.
• Use of hormonal agents with anti-tumor activity against prostate cancer including 5-alpha reductase inhibitors, androgens (e.g., testosterone), cytoproterone acetate, progestational agents, and estrogens/diethylstilbestrol within 28 days prior to the start of study treatment.
• Use of herbal products or alternative therapies that may decrease PSA levels or that may have hormonal anti-prostate cancer activity (e.g., saw palmetto, PC-SPES, PC-HOPE, St. John's wort, selenium supplements, grape seed extract, etc.) within 28 days of study treatment initiation or plans to initiate treatment with these products/alternative therapies during the entire duration of the study.
• Participants receiving a blood transfusion within 14 days of randomization are not eligible.
• History of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of randomization.
• Medical conditions such as uncontrolled hypertension as indicated by a resting systolic blood pressure \> 160 mm Hg or diastolic blood pressure \> 90 mm Hg at screening, uncontrolled diabetes mellitus, and cardiac disease that would preclude participation, as determined by the investigator.
• Untreated known or suspected brain metastases or spinal cord compression or clinically significant malignant epidural disease.

Sponsors & Collaborators

• Prostate Cancer Clinical Trials Consortium: lead
• Pfizer: collaborator
• Dana-Farber Cancer Institute: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms; Adenocarcinoma

Interventions

talazoparib; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Alicia Morgans, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah Wise

CONTACT

215-380-9051; wises@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: February 25, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2030
• Last Updated: April 24, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF

Locations

US (2)