Phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with androgen receptor pathway inhibitors in patients with metastatic hormone-sensitive prostate cancer with and without homologous recombination repair mutation (EvoPAR-Prostate01).
Authors: Azad Arun , Agarwal Neeraj , Armstrong Andrew J. , Hellmis Eva , Schlürmann Friederike , Sugimoto Mikio , Ürün Yüksel , Xing Nianzeng , Aregay Mehreteab , Lima Julianne , Meulendijks Didier , Chi Kim N. 
Published: February 2025

TPS279

Background:
PARP inhibitors (PARPi) in combination with androgen receptor pathway inhibitors (ARPIs) are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). PARPi utilization in earlier lines of treatment may result in greater magnitude of benefit. Saruparib is a potential best-in-class PARPi, which selectively inhibits and traps PARP1, has minimal effect on PARP2, and hence may offer an improved therapeutic window compared with currently approved nonselective PARPi. The efficacy and safety of saruparib plus ARPIs for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and mCRPC are being assessed in the phase I/IIa PETRANHA study (NCT05367440). The phase III EvoPAR-Prostate01 study (NCT06120491) is evaluating the efficacy and safety of saruparib plus physician’s choice of ARPI (abiraterone, darolutamide, or enzalutamide) compared with placebo plus physician’s choice of ARPI in participants with mHSPC.
Methods:
This is a 2-cohort, 2-arm, randomized, double-blind, placebo-controlled, multicenter global study. Key eligibility criteria include age ≥18 years, histologically confirmed mHSPC (
de novo
or recurrent low- or high-volume disease), ECOG PS 0-1, and confirmed, prospectively defined homologous recombination repair gene mutation (HRRm) status (defined by the presence/absence of pathogenic/likely pathogenic mutations in ≥1 of the genes
BRCA1
,
BRCA2
,
ATM
,
CDK12
,
PALB2
,
RAD51B
,
RAD51C
,
RAD51D
, and
BARD1
). Participants must be receiving androgen deprivation therapy throughout the study or have undergone bilateral orchiectomy, and must be suitable for treatment with ARPIs. Key exclusion criteria include prior therapy with PARPi, prior chemotherapy or ARPIs in the mHSPC setting (prior ARPIs for localized disease permitted), and history of, or suspected, myelodysplastic syndrome/acute myeloid leukemia. Participants are allocated to either the HRRm or non-HRRm cohort based on prospective testing of both tumor tissue and circulating tumor DNA. Participants are randomized 1:1 to receive saruparib plus physician’s choice of ARPI or placebo plus physician’s choice of ARPI. Treatment continues until disease progression, unacceptable toxicity, or participant-initiated withdrawal. The primary endpoint is radiographic progression-free survival (rPFS), with overall survival (OS) a key secondary endpoint. Planned statistical analyses of rPFS and OS will be conducted within each cohort using a stratified log-rank test. Approximately 1,800 participants (550 HRRm; 1,250 non-HRRm) will be randomized. Enrollment began in November 2023 and is ongoing. Clinical trial information:
NCT06120491
.