(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, will host the Prostate, Testicular, and Penile Cancer – Posters Session. Dr. Karen A. Autio will present Abstract TPS5145: TALENT: A randomized phase 2 study of talazoparib +/- enzalutamide in patients with metstatic castration resistant prostate cancer (mCRPC) and HRR alterations after progression on abiraterone acetate.
The phase 3 TALAPRO-2 trial previously demonstrated improved outcomes with enzalutamide plus talazoparib compared with enzalutamide alone in patients with HRR-mutated mCRPC.1 However, only a small proportion of patients enrolled in TALAPRO-2 had prior exposure to abiraterone acetate and prednisone, and none had previously received an androgen receptor inhibitor in earlier disease settings.1 Given the rapidly evolving treatment landscape in metastatic hormone-sensitive prostate cancer (mHSPC), many patients now receive intensified hormonal therapy with ADT plus abiraterone earlier in the disease course, raising important questions regarding the efficacy of subsequent PARP inhibitor and AR pathway inhibitor combinations after progression on abiraterone.
The TALENT trial (NCT06844383) was designed to address this increasingly relevant clinical scenario by evaluating whether the synergistic interaction between PARP inhibition and androgen receptor blockade is maintained in patients with HRR-mutated mCRPC whose disease has already demonstrated resistance to androgen biosynthesis inhibition with abiraterone acetate and prednisone.
TALENT is a randomized phase II study expected to enroll approximately 126 patients with HRR-mutated mCRPC who experienced disease progression while receiving abiraterone acetate for hormone-sensitive or locally advanced disease. Eligible patients must harbor a confirmed alteration in one of 12 predefined HRR genes, although ATM-mutated tumors are capped at 15% of enrollment. Prior docetaxel exposure in the mHSPC setting is permitted and incorporated as a stratification factor.
Patients are randomized in a 1:1 fashion to receive either talazoparib plus enzalutamide or talazoparib monotherapy, both administered in combination with ongoing ADT. Treatment continues until radiographic or clinical progression, unacceptable toxicity, prolonged treatment interruption, withdrawal of consent, investigator decision, or death.
Disease assessments are performed using RECIST 1.1 criteria along with PCWG3 criteria for bone disease evaluation. The primary endpoint is investigator-assessed radiographic progression-free survival (rPFS).
Key secondary endpoints include:
- Time to PSA50 response
- Time to PSA progression
- Overall survival
- Patient-reported quality-of-life outcomes
Importantly, the study also includes exploratory analyses evaluating rPFS outcomes according to HRR subgroup, including BRCA versus non-BRCA alterations, individual gene-level analyses, and broader gene clusters.
The trial is planned across approximately 15 sites in the United States. As of January 27, 2026, no patients had yet been enrolled.
Presented by: Karen Autio, MD, MSc, Memorial Sloan Kettering Cancer Center, New York, NY, United States of America
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
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