Phase III study of talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): TALAPRO-2 (TP-2) China cohort

BackgroundTP-2 (NCT03395197) demonstrated improved radiographic progression-free survival (rPFS) for the all-comers cohort of pts with mCRPC (with/without alterations in homologous recombination repair [HRR] genes) who received 1L TALA + ENZA vs PBO + ENZA (not reached vs 21.9 mo, respectively; HR 0.63; 95% CI, 0.51–0.78; P<0.0001). We present the TP-2 China cohort analysis.MethodsThe China cohort includes pts from the all-comers cohort and China extension (unselected HRR gene status). Pts had asymptomatic/mildly symptomatic mCRPC, received ongoing androgen deprivation therapy, and were prospectively tested for HRR alterations in tumor tissue. Pts were randomized 1:1 to TALA 0.5 mg/day (moderate renal impairment 0.35 mg/day) or PBO; all received ENZA 160 mg/day. Primary endpoint: rPFS by BICR. Secondary endpoints included overall survival (OS), objective response rate (ORR), ≥50% PSA response, safety, and pt-reported outcomes.ResultsData cutoff (China cohort): Nov 15, 2023 (N=125; TALA + ENZA, N=63 [HRR-deficient, n=14]; PBO + ENZA, N=62, [HRR-deficient, n=11]). TALA + ENZA improved median rPFS vs PBO + ENZA (33.3 vs 10.9 mo, respectively; HR 0.30; 95% CI, 0.17–0.56; P<0.0001). rPFS for HRR-deficient pts was 15.7 vs 4.0 mo, respectively (HR 0.16; 95% CI, 0.04–0.64; P=0.0044); 35.9 vs 13.8 mo (HR 0.36; 95% CI, 0.18–0.70; P=0.0018) for HRR non-deficient/unknown. Though OS data are immature (TALA + ENZA, 25 deaths; PBO + ENZA, 34), interim OS data favored TALA + ENZA (36.9 mo) vs PBO + ENZA (24.1 mo; HR 0.50; 95% CI, 0.29–0.87; P=0.013). ORR also favored TALA + ENZA (50.0%) vs PBO + ENZA (31.6%), as did ≥50% PSA response rate (TALA + ENZA 77.0%; PBO + ENZA 54.2%). In the TALA + ENZA arm, all pts had ≥1 adverse event (AE) and 79.4% had grade 3–4 AEs; anemia was the most common AE. AEs led to discontinuation of TALA/PBO only in 11.1% of pts in the TALA + ENZA arm and 4.8% in the PBO + ENZA arm. No significant differences in overall GHS/QoL were observed between arms.ConclusionsIn keeping with the TP-2 all-comers cohort, TALA + ENZA demonstrated clinically meaningful improvement in rPFS vs PBO + ENZA for the China cohort. No new safety signals were identified.Clinical trial identificationNCT03395197.Editorial acknowledgementMedical writing support was provided by Emily Messina, PhD, and Ann Gordon, PhD, CMPP of CMC Affinity, a division of IPG Health Medical Communications, and was funded by Pfizer. Pfizer’s generative artificial intelligence tool MAIA (Medical Artificial Intelligence Assistant) was used in the production of the first draft of this abstract to suggest content. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.Legal entity responsible for the studyPfizer is responsible for the governance, coordination, and running of the study.FundingThis study was funded by Pfizer Inc. Astellas Pharma Inc. provided enzalutamide.DisclosureH. Ye, H. Zhao, Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc.; Financial Interests, Personal, Stocks or ownership: Pfizer Inc. All other authors have declared no conflicts of interest.