TPS5145 Background: The phase 3 TALAPRO-2 study (NCT03395197) demonstrated superior efficacy with enzalutamide plus talazoparib vs. enzalutamide plus placebo for pts with mCRPC with tumors harboring HRR mutations. Only 8% of HRRm pts enrolled in TALAPRO-2 had prior exposure to abiraterone acetate with prednisone, and none had received an androgen receptor inhibitor. Given the evolving treatment landscape of metastatic hormone sensitive prostate cancer (mHSPC), many patients now receive ADT in combination with abiraterone acetate and prednisone until progression. It is unknown whether the synergistic effects of inhibiting PARP alongside potent AR inhibition will be maintained in those patients with tumors that have demonstrated resistance to an androgen biosynthesis inhibitor such as abiraterone. The TALENT study (NCT06844383) will address this unanswered question by randomizing pts with HRR-mutated mCRPC following progression on abiraterone acetate with prednisone to receive talazoparib in combination with enzalutamide versus talazoparib alone. We hypothesize that synergy between PARP and AR inhibition will be demonstrated in this contemporary patient population. Methods: TALENT will enroll approximately 126 pts with mCRPC with prior disease progression while receiving abiraterone acetate for HSPC or locally advanced disease and a confirmed mutation in one of twelve HRR genes. ATM mutations will be limited to 15%. Prior exposure to docetaxel in the mHSPC setting will be included as a stratification factor. Pts will be randomized in a 1:1 fashion to either talazoparib and enzalutamide or talazoparib alone administered along with ADT. Pts will continue treatment until disease progression, unacceptable toxicity, treatment delay > 60 days of talazoparib, protocol violation, withdrawal of consent, physician decision, study termination by the Sponsor, loss to follow-up, or death. Patients will be monitored using RECIST 1.1 and PCWG3 criteria for bone disease. The primary endpoint is investigator-assessed radiographic progression free survival (rPFS). Secondary endpoints include time to PSA50 response, time to PSA progression, overall survival, and patient reported outcomes capturing quality of life. Exploratory analyses will evaluate rPFS by HRR gene (BRCA vs non-BRCA, individual genes, and gene clusters). Pt recruitment is planned at approximately 15 sites in the US . As of January 27, 2026, 0 pts have been enrolled. Clinical trial information: NCT06844383 .
Autio et al. (Thu,) studied this question.