Saruparib in Combination With Physician's Choice of ARPI in Patients With mHSPC Previously Treated With Docetaxel or 177Lu-PSMA Therapy Without Disease Progression and PSA ≥ 0.2 ng/mL (EvoPAR-PR05) (EvoPAR-PR05)

A Randomized, Double-Blind, Placebo-Controlled, 2-Cohort, Phase III Study of Saruparib Combined With Physician's Choice of Androgen Receptor Pathway Inhibitor in Patients With Metastatic Hormone-Sensitive Prostate Cancer, Previously Treated With Docetaxel or PSMA-directed 177Lutetium-Containing Therapy Without Disease Progression, and With Prostate-Specific Antigen ≥ 0.2 ng/mL: EvoPAR-Prostate05

The primary objective of this study is to measure efficacy of saruparib + physician's choice of ARPI compared with placebo + ARPI in men with metastatic hormone-sensitive prostate cancer (mHSPC) who have previously received docetaxel chemotherapy or a prostate-specific membrane antigen (PSMA)-directed lutetium-177 radioligand therapy with no evidence of disease progression and PSA ≥ 0.2 ng/mL.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
• Intervention / Treatment: Drug: Saruparib; Drug: Enzalutamide; Drug: Darolutamide; Drug: Abiraterone; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 1330
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 7W9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be ≥ 18 at the time of signing the informed consent.
• Histologically documented diagnosis of prostate adenocarcinoma that is de novo or recurrent and hormone-sensitive.
• Metastatic disease confirmed prior to initiation of previous treatment with docetaxel or Lu-PSMA-containing regimens for mHSPC.
• Previous treatment with docetaxel (IV, Q3w)- or Lu-PSMA (IV, Q6w) with last dose within past 6 months.

• Participants must have the following:

  • Must be receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy.
  • Had no evidence of disease progression
  • Had all toxicities related to docetaxel- or Lu-PSMA-containing treatment (except for alopecia and peripheral neuropathy) resolved to CTCAE Grade 1 or lower.
• PSA ≥ 0.2 ng/mL within 14 days prior to randomization.
• Serum testosterone < 1.7 nmol/L or 50 ng/dL.
• Palliative radiotherapy for symptoms management will be permitted and is to be completed at least 4 weeks prior to randomization for wide field radiation therapy and at least 2 weeks prior to randomization for limited field radiation therapy.
• Provision of a FFPE tumor tissue sample and a blood sample (for ctDNA).
• Confirmed HRRm, HRD and PTEN status.
• Adequate organ and bone marrow function.
• Minimum life expectancy of 6 months.
• Male, assigned at birth, inclusive of all gender identities.
• Contraceptive use by participants or participant partners should be consistent with local regulations.
• Capable of giving signed informed consent.
• - -

Exclusion Criteria:

• Hypersensitivity to saruparib, ARPI or any excipients of these products or any contraindication or restriction based on the local label.
• Any history of persisting (> 2 weeks) severe cytopenia due to any cause (eg, ANC< 0.5 × 10^9/L or platelets < 50 × 10^9/L)
• Any known predisposition to bleeding (eg, active peptic ulceration, recent [within6 months] hemorrhagic stroke, proliferative diabetic retinopathy.
• Spinal cord compression or brain metastases unless asymptomatic and stable.
• History of MDS/AML or with features suggestive of MDS/AML
• History of another primary malignancy, with some exceptions.
• Any chronic gastrointestinal diseases or conditions including inability to swallow the formulated product that would preclude adequate absorption of any study drug.
• History of seizure or predispose to seizure, including any history of loss of consciousness or transient ischemic attack within 12 months of enrolment.
• Serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• Major surgical procedure or significant traumatic injury within 4 weeks of the first dose or an anticipated need for major surgery during the study.
• Switched ARPI agent in previous treatment for mHSPC due to disease progression. Note: if the ARPI agent was switched due to any reason other than disease progression and switch was prior to ICF signature, participants will be eligible.
• Any prior treatment with a PARPi or platinum chemotherapy.
• - -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone; Saruparib 60 mg + ARPI (enzalutamide, darolutamide, or abiraterone) : Participants will receive saruparib 60 mg orally once daily in combination with physician's choice of ARPI in cycles of 28 days	Drug: Saruparib; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone); Drug: Enzalutamide; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI; Drug: Darolutamide; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI; Drug: Abiraterone; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI
Placebo Comparator: Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone; Placebo + ARPI (enzalutamide, darolutamide, or abiraterone): Participants will receive placebo orally once daily in combination with physician's choice of ARPI in cycles of 28 days	Drug: Enzalutamide; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI; Drug: Darolutamide; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI; Drug: Abiraterone; Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI; Other: Placebo; Arm 2: Placebo + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression-free survival (rPFS)	Radiographic PFS (rPFS) is the primary endpoint of this study, defined as the time from randomization to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or death due to any cause.	Up to approximately 56 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic progression-free survival (rPFS)	Radiographic PFS (rPFS) is the primary endpoint of this study, defined as the time from randomization to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or death due to any cause.	Up to approximately 56 months
Overall Survival (OS)	OS is defined as the time from the date of randomization until death due to any cause.	Up to approximately 80 months
Time to Second Progression or Death (PFS2)	PFS2 is defined as the time from randomization to the earliest progression (defined as radiographic progression, clinical progression, or PSA progression) after initiation of first subsequent treatment following the initial investigator-assessed progression or death (ie, date of PFS2 event or censoring - date of randomization + 1).	Up to approximately 56 months
Time to First Subsequent Therapy or Death (TFST)	TFST is defined as the time from randomization to the start date of the first subsequent anticancer therapy after discontinuation of randomized treatment, or death due to any cause (ie, date of first subsequent cancer therapy or death - date of randomization + 1).	Up to approximately 56 months
Symptomatic Skeletal Event-free Survival (SSE-FS)	SSE-FS is defined as the time from the date of randomization to the earliest of the following: Use of radiation therapy to prevent or relieve skeletal symptoms.; Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiographic documentation is required. A pathological fracture, as determined by investigator, is defined as associated with low or no trauma and deemed to have occurred at a site of bone metastasis.; Occurrence of spinal cord compression. Radiographic documentation is required.; Orthopedic surgical intervention for bone metastasis.; Death due to any cause.	Up to approximately 56 months
Time to Castration Resistance (TTCR)	TTCR is defined as the time from randomization to the first castration-resistant event (radiographic disease progression, PSA progression per PCWG3, or SSE, whichever occurs first, with castrate levels of testosterone below 50 ng/dL).	Up to approximately 56 months
Time to PSA progression	Time to PSA progression, defined as the time from randomization to PSA progression per PCWG3 criteria.	Up to approximately 56 months
Time to deterioration in physical function (TTDPF)	TTDPF is defined as the time from randomization to deterioration in PROMIS SF-PF scores.	Up to approximately 56 months
Time to pain progression (TTPP)	TTPP is defined as the time from randomization to clinically meaningful pain progression based on a 2-point increase from baseline in the BPI-SF Item 3 'worst pain in 24 hours' score and/or initiation of/increase in opioid analgesic use.	Up to approximately 56 months
Brief Pain Inventory - Short Form (BPI-SF)	Change from baseline in BPI-SF worst pain score, pain severity and interference domain scores.	Up to approximately 56 months
Time to deterioration in urinary symptoms (TTDUS)	TTDUS is defined as the time from randomization to deterioration in the EORTC QLQ-PR25(US) subscale scores.	Up to approximately 56 months
Plasma concentrations of AZD5305	To assess PK of AZD5305 in plasma	Day 1 of Cycle 1, Cycle 2 and Cycle 3 (each cycle is of 28 days)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 17, 2031
• Study Completion (Estimated): June 14, 2033

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Docetaxel; Metastatic prostate cancer; Prostate Cancer; mHSPC; AZD5305; PARPi; Hormone sensitive prostate cancer; Castration sensitive; Saruparib; HRRm; non-HRRm; PSA>0.2ng/ml; Androgen pathway modulation sensitive (APMS); PSMA-directed 177Lutetium
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; darolutamide; abiraterone; enzalutamide
• Other Study ID Numbers: D972DC00001; 2026-526275-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No