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)

NCT07711002 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: D972DC000012026-526275-38-00
• Study Type: interventional
• Target: 1,330
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

Keywords

Saruparib; HRRm; non-HRRm; mHSPC; Prostate Cancer; AZD5305; PSA>0.2ng/ml; Androgen pathway modulation sensitive (APMS); Castration sensitive; Metastatic prostate cancer; Hormone sensitive prostate cancer; PARPi; Docetaxel; PSMA-directed 177Lutetium

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Overall Survival (OS)

  Up to approximately 80 months

• Radiographic progression-free survival (rPFS)

  Up to approximately 56 months

• Time to Second Progression or Death (PFS2)

  Up to approximately 56 months

• Time to First Subsequent Therapy or Death (TFST)

  Up to approximately 56 months

• Symptomatic Skeletal Event-free Survival (SSE-FS)

  Up to approximately 56 months

Study Arms (2)

Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

EXPERIMENTAL

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; Drug: Enzalutamide; Drug: Darolutamide; Drug: Abiraterone

Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

PLACEBO COMPARATOR

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

Other: Placebo; Drug: Enzalutamide; Drug: Darolutamide; Drug: Abiraterone

Interventions

Saruparib DRUG

Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)

Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

Placebo OTHER

Arm 2: Placebo + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone)

Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

Enzalutamide DRUG

Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI

Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone; Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

Darolutamide DRUG

Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI

Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone; Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

Abiraterone DRUG

Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI

Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone; Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \- -

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Ottawa, Ontario, K1H 7W9, Canada

Location

Research Site

Montreal, Quebec, H2X 0A9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; darolutamide; abiraterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 17, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 17, 2031
• Study Completion (Estimated): June 14, 2033
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

CA (2)