Saruparib in combination with androgen receptor pathway inhibitors in metastatic hormone-sensitive prostate cancer - Clinical trial protocol - EvoPAR-Prostate01

Sep 23, 2026

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 trial evaluating saruparib plus ARPIs in metastatic hormone-sensitive prostate cancer with and without homologous recombination repair gene mutations, under mandatory androgen deprivation therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

1. Introduction

1.1. Current treatment approaches for metastatic prostate cancer

FUTURE ONCOLOGY 2026, VOL. 22, NO. 10, 1153–1163 [https://doi.org/10.1080/14796694.2026.2655433](https://doi.org/10.1080/14796694.2026.2655433) | CLINICAL TRIAL PROTOCOL
Saruparib in combination with androgen receptor pathway inhibitors in metastatic hormone-sensitive prostate cancer: EvoPAR-Prostate01
Arun A. Azad a, Neeraj Agarwalb, Andrew J. Armstrongc, Eva Hellmisd, Mikio Sugimotoe, Yüksel Ürünf, Nianzeng Xingg, Mehreteab Aregayh, Julianne Limai, Didier Meulendijksj and Kim N. Chi k
aDepartment of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; bDivision of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA; cDepartment of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University Medical Center, Durham, NC, USA; dUrologicum Duisburg, Center for Urology and Urologic Cancer, Duisburg, Germany; eDepartment of Urology, Kagawa University, Kagawa, Japan; fDepartment of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey; gDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; hGlobal Medicines Development, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA; iGlobal Medicines Development, Oncology R&D, AstraZeneca, Cambridge, UK; jGlobal Medicines Development, Oncology R&D, AstraZeneca, Barcelona, Spain; kDepartment of Medical Oncology, University of British Columbia, Vancouver, BC, Canada | | | | --- | --- | --- | | 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 . EvoPARProstate01 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:](registration: www.clinicaltrials.gov)[ www.clinicaltrials.gov](registration: www.clinicaltrials.gov) identifier is NCT06120491; EU CT number is 2023- 504214-30-00. | | ARTICLE HISTORY
Received 13 February 2026 Accepted 31 March 2026
KEYWORDS
Saruparib; AZD5305; PARP inhibitor; PARP1 selective; metastatic hormonesensitive prostate cancer; homologous recombination repair mutation | | 1. Introduction
1.1. Current treatment approaches for metastatic prostate cancer
Prostate cancer is the second most commonly diagnosed cancer in men, and in 2022, it was the 5th most common cause of cancer-related death in men worldwide, accounting for 396,792 deaths [1] . In low- and middle-income countries, up to 43% of patients present with metastatic (

FAQs

What is EvoPAR-Prostate01 evaluating in metastatic hormone-sensitive prostate cancer?

EvoPAR-Prostate01 evaluates the efficacy and safety of saruparib combined with androgen receptor pathway inhibitors (ARPIs) versus placebo combined with ARPI in metastatic hormone-sensitive prostate cancer.

How are participants classified and randomized in the study?

Participants are randomized 1:1 into two cohorts based on prospectively defined homologous recombination repair gene mutation status (HRRm vs non-HRRm) and receive either saruparib plus physician’s-choice ARPI or placebo plus ARPI.

What are the primary and key secondary endpoints?

The primary endpoint is radiographic progression-free survival (rPFS). Overall survival (OS) is a key secondary endpoint.

Sep 23, 2026

Uploaded by Aria Callaghan