TALAPRO-3: Talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations.

LBA5007 Background: In the Phase 3 TALAPRO-2 trial, adding the poly(ADP-ribose) polymerase inhibitor TALA to the androgen-receptor pathway inhibitor (ARPI) ENZA significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) in pts with metastatic castration-resistant prostate cancer (mCRPC), with the HRR-deficient cohort experiencing the greatest benefit. The TALAPRO-3 trial investigates the efficacy and safety of TALA + ENZA in men with mCSPC bearing HRR gene alterations. Methods: In the Phase 3, double-blind TALAPRO-3 trial, pts were randomized 1:1 to TALA 0.5 mg (0.35 mg if moderate renal impairment) or PBO plus ENZA 160 mg once daily, stratified by de novo vs relapsed mCSPC, high- vs low-volume disease, and BRCA vs non- BRCA mutational status. Key eligibility criteria are ECOG PS 0 or 1, presence of HRR gene alteration(s) ( ATM , ATR , BRCA1 , BRCA2 , CDK12 , CHEK2 , FANCA , MLH1 , MRE11A , NBN , PALB2 , RAD51C ) confirmed by tumor tissue and/or circulating tumor DNA testing, ongoing androgen deprivation therapy (ADT), no prior treatment with docetaxel (protocol amendment in Sept 2021), and ≤3 mo of ADT with or without an approved ARPI for mCSPC. Primary endpoint is investigator-assessed rPFS; OS is the alpha-protected key secondary endpoint. Results: 599 pts were randomized (300 to TALA + ENZA; 299 to PBO + ENZA). At a median follow-up of 37.6 mo (TALA + ENZA) and 37.7 mo (PBO + ENZA) at data cutoff (Feb 18, 2026), TALA + ENZA significantly improved rPFS vs PBO + ENZA (HR, 0.481; 95% CI, 0.357–0.647; 2-sided P