Saruparib for Prostate Cancer

(EvoPAR-PR02 Trial)

Recruiting at 235 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Androgen deprivation therapy

Must not be taking: Chemotherapy, Immunotherapy, PARP inhibitors

Disqualifiers: MDS/AML, Bleeding predisposition, Cardiac issues, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 93 months

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called Saruparib for men with high-risk or very high-risk prostate cancer linked to a specific genetic mutation (BRCA1 or BRCA2) associated with breast cancer. The researchers seek to determine if adding Saruparib to standard treatments like radiation and hormone therapy can prevent cancer from spreading. Participants should be newly diagnosed or have a high-risk recurrence after surgery, with confirmed BRCA mutation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using strong inducers and inhibitors of CYP3A4 (a liver enzyme) and certain herbal supplements at least 21 days before starting the study. You also need to avoid drugs that prolong QT interval, which can affect heart rhythm.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Saruparib has been tested for its effects and safety in people with advanced prostate cancer. In earlier studies, Saruparib showed promising results. Patients generally tolerated it well, with manageable side effects. In one study, patients taking Saruparib experienced tumor shrinkage, and the overall response was positive.

Most side effects were mild to moderate, meaning they weren't too severe. These included tiredness, nausea, and some changes in blood counts. These findings suggest that Saruparib might be safe for people, but like all medications, it can have side effects. Discuss these possibilities with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about Saruparib for prostate cancer because it targets a specific enzyme called PARP, which is crucial in repairing damaged DNA in cancer cells. This is different from most standard treatments that usually rely on hormone therapies like androgen deprivation therapy (ADT) or drugs like abiraterone. By inhibiting PARP, Saruparib may prevent cancer cells from fixing themselves, potentially leading to more effective cancer cell death. Moreover, when combined with other therapies such as ADT and abiraterone, Saruparib might enhance the overall treatment effect, offering hope for improved outcomes in patients with advanced prostate cancer.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that Saruparib, a new drug, holds promise for treating prostate cancer. In this trial, some participants will receive Saruparib alongside other prostate cancer treatments. Earlier studies demonstrated that when combined with other prostate cancer drugs, Saruparib led to a response in about 9 out of 10 patients with advanced prostate cancer. This drug blocks a protein called PARP1, preventing cancer cells from repairing themselves. Early results also suggest that Saruparib might be safer and more effective than older treatments. Overall, the findings are encouraging for people with prostate cancer, especially those with certain genetic mutations. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

Men with high-risk, localized or locally advanced prostate cancer who have a BRCA mutation can join this trial. They must be suitable for standard radiation and hormone therapy but cannot participate if they've had previous treatments that could affect the study's results.

Inclusion Criteria

Participants must not father children or donate sperm from signing informed consent form (ICF), during the study intervention and for 6 months after the last dose of study intervention

Minimum life expectancy of 12 months

Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample

Exclusion Criteria

I do not have an active tuberculosis infection.

I have had severe low blood cell counts for more than 2 weeks.

I cannot take pills due to severe nausea, vomiting, gut diseases, or major bowel surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive saruparib or placebo with ADT (+ abiraterone) in a randomized, double-blind manner

93 months

Day 1 of Cycle 1, Cycle 3, and Cycle 6 (each cycle is of 28 days)

Follow-up

Participants are monitored for metastasis-free survival and overall survival

Up to approximately 11 years

What Are the Treatments Tested in This Trial?

Interventions

• Saruparib

Trial Overview The trial is testing whether adding Saruparib to standard radiation and hormone therapy improves metastasis-free survival compared to a placebo in men with BRCA-mutated prostate cancer.

How Is the Trial Designed?

Group I: Cohort B: Saruparib (AZD5305) + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) Experimental Treatment 3 Interventions

Participants will receive saruparib, abiraterone and prednisolone/prednisone along with ADT.

Group II: Cohort A: Saruparib (AZD5305) + Physician's Choice ADT Experimental Treatment 2 Interventions

Participants will receive saruparib along with ADT.

Group III: Cohort A: Placebo + Physician's Choice ADT Placebo Group 2 Interventions

Participants will receive matching placebo to saruparib along with ADT.

Group IV: Cohort B: Placebo + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) Placebo Group 3 Interventions

Participants will receive matching placebo to saruparib, abiraterone and prednisolone/prednisone along with ADT.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

A phase II trial indicates that the combination of the antiandrogen abiraterone and the PARP inhibitor olaparib significantly enhances progression-free survival in patients with metastatic castration-resistant prostate cancer.

This benefit occurs regardless of the patients' homologous recombination repair-mutation status, suggesting a broad applicability of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone-Olaparib Combo Aids Men with mCRPC. [2019]

In the Phase III PROfound study, olaparib demonstrated improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to control treatments in Asian patients with metastatic castration-resistant prostate cancer, particularly in those with BRCA gene alterations.

The safety profile of olaparib in the Asian subset was consistent with the global population, showing no new safety concerns, indicating it is a well-tolerated treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis. Matsubara, N., Nishimura, K., Kawakami, S., et al.[2023]

In a phase II trial involving 88 patients with metastatic castration-resistant prostate cancer, danusertib showed minimal efficacy, with only one patient in each treatment group achieving a PSA response after 3 months.

The treatment was generally well tolerated, but neutropenia was a significant side effect, affecting 37.2% of patients in the 6-hour infusion group and 15.8% in the 24-hour infusion group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. Meulenbeld, HJ., Bleuse, JP., Vinci, EM., et al.[2021]

Citations

1. targetedonc.com targetedonc.com/view/saruparib-plus-arpi-shows-promising-efficacy-in-metastatic-prostate-cancer

Saruparib Plus ARPI Shows Promising Efficacy in ... Data from the efficacy-evaluable population showed that objective response rates were 88.5% (23/26) in patients with metastatic castration- ...

2. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164003-esmo-2025-first-interim-efficacy-analysis-of-the-phase-1-2-petranha-trial-of-saruparib-androgen-receptor-pathway-inhibitors-arpi-in-patients-pts-with-metastatic-prostate-cancer-mpc.html

First Interim Efficacy Analysis of the Phase 1/2 PETRANHA ... Saruparib (AZD5305) is a next-generation, PARP1-selective inhibitor with preclinical data indicating greater target engagement, efficacy, and safety compared ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS279

Phase III, double-blind, placebo-controlled, 2-cohort, ... 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 ...

4. urologytimes.com urologytimes.com/view/parp1-selective-inhibitor-arpi-combination-is-well-tolerated-in-advanced-prostate-cancer

PARP1-selective inhibitor/ARPI combination is well ... Saruparib combined with ARPIs demonstrates promising safety and efficacy in metastatic prostate cancer, with manageable toxicity and high ...

5. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-024-01370-z

The PARP1 selective inhibitor saruparib (AZD5305) elicits ... Results. AZD5305 showed superior antitumor activity than the first-generation PARPi in terms of preclinical complete response rate (75% vs. 37%) ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.123

PETRANHA: Phase 1/2 study of AZD5305 + novel ... DDIs were evaluated for each combination. Results: At data cutoff (July 10, 2023), 48 pts were included in the interim safety analysis (Arm 1, n ...

7. cancernetwork.com cancernetwork.com/view/saruparib-shows-favorable-activity-safety-in-mutant-advanced-solid-tumors

Saruparib Shows Favorable Activity, Safety in Mutant ... Saruparib at 20 mg once daily yielded a median best change in tumor size of –22.1% (range, –91.2% to 133.3%), an overall response rate (ORR) of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06120491

Study Details | NCT06120491 | Saruparib (AZD5305) vs ... The intention of the study is to demonstrate superiority of Saruparib (AZD5305) + physician's choice NHA relative to placebo + physician's choice NHA by ...