Abstract
Poly(ADP-ribose) polymerase (PARP) inhibitor plus androgen receptor pathway inhibitor (ARPI) is approved for selected patients with metastatic castration-resistant prostate cancer. Saruparib (AZD5305) is a new-generation PARP inhibitor that selectively inhibits and traps PARP1. EvoPAR-Prostate01 is a Phase III, 2-cohort, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of saruparib plus ARPIs in participants with histologically confirmed metastatic hormone-sensitive prostate cancer (mHSPC) with and without confirmed, prospectively defined, homologous recombination repair gene mutations (HRRm). Participants must receive androgen deprivation therapy throughout the study, or have undergone bilateral orchiectomy, and be suitable for ARPI. Key exclusion criteria include prior PARP inhibitor, prior chemotherapy or ARPI in the mHSPC setting (prior ARPI for localized disease is permitted), and history of/suspected myelodysplastic syndrome/acute myeloid leukemia. Approximately 1800 participants (550 HRRm; 1250 non-HRRm) are randomized 1:1 to receive either saruparib plus physician's choice of ARPI (abiraterone plus prednisone/prednisolone, darolutamide, or enzalutamide) or placebo plus ARPI. Treatment beyond disease progression and crossover between cohorts are not permitted. The primary endpoint is radiographic progression-free survival (rPFS); overall survival (OS) is a key secondary endpoint. Analyses of rPFS and OS will be conducted within each cohort by stratified log-rank test. Enrollment began in November 2023.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06120491; EU CT number is 2023-504214-30-00.