A study to evaluate the impact on metastases-free survival with the addition of saruparib vs placebo to a standard radiotherapy androgen deprivation regimen in men with high-risk prostate cancer with a BRCA mutation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

10 Dec 2025 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-513586-39-00

ClinicalTrials.gov

NCT06952803

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The purpose of the study is to demonstrate superiority of Saruparib (AZD5305) relative to placebo added to a standard radiation therapy (RT) + androgen deprivation therapy (ADT) regimen by assessment of metastases-free survival in participants with high-risk and very high-risk localised/locally advanced prostate cancer with a breast cancer gene mutation (BRCAm).

Conditions and MedDRA coding

Prostate Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003447-PIP01-23

Plan to share 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. All requests will be evaluated as per the AZ disclosure commitment https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male participants with a histologically documented diagnosis of prostate adenocarcinoma.
2. Newly diagnosed high-risk and very high-risk (localised/locally advanced) prostate cancer or a high-risk biochemical recurrence (BCR) following radical prostatectomy.
3. Provision of a formalin fixed and paraffin embedded (FFPE) tumour tissue sample.
4. Confirmed BRCA1 or BRCA2 mutation status by central tumour tissue is required for enrolment.
5. Participants required to have a computed tomography (CT) or magnetic resonance imaging (MRI) and a bone scan following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
6. Participants required to have a prostate-specific membrane antigen-positron emission tomography (PSMA-PET) following the completion of their planned RT. This screening scan must confirm no evidence of disease or evidence of disease confined to the pelvis (M0).
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomization.
8. Minimum life expectancy of 12 months.
9. Adequate organ and bone marrow function as described in study protocol.
10. All participants will have received either primary or salvage RT. Radiotherapy administered to the prostate (± pelvis) either in the primary or salvage setting must be delivered with curative intent. Use of metastases-directed therapy, as part of the RT radiation plan, is permitted as localized RT treatment for a metastatic lesion(s) outside the pelvis.
11. All participants will have received a planned regimen of ADT with a gonadotropin releasing hormone (GnRH) analogue.
12. 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.
13. Participants must use a condom (with spermicide - where permitted) from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.

Exclusion criteria 15

1. Participants with a history of myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
2. Participants with any known predisposition to bleeding [e.g., active peptic ulceration, recent (within 6 months) hemorrhagic stroke, proliferative diabetic retinopathy].
3. Any history of persisting (> 2 weeks) severe cytopenia due to any cause.
4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of saruparib and/or abiraterone.
5. History of another primary malignancy, with exceptions.
6. Persistent toxicities [Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2] caused by previous anticancer therapy.
7. Cardiac criteria, including history of arrhythmia and cardiovascular disease.
8. Evidence of active and uncontrolled hepatitis B and/or hepatitis C.
9. Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection.
10. Active tuberculosis infection.
11. Any prior chemotherapy (i.e., docetaxel) or immunotherapy; any prior treatment with a poly (ADP-ribose) polymerase (PARP) inhibitor.
12. Prior treatment within 14 days with blood product support or growth factor support.
13. Concomitant use of strong inducers and inhibitors of CYP3A4 (applies to saruparib and abiraterone) or herbal supplements within 21 days or at least 5 half-lives (whichever is longer), of randomization.
14. Concomitant use of drugs that are known to prolong QT and have a known risk of Torsades de Pointes (TdP).
15. Participants with a known hypersensitivity to saruparib or any excipients of these products.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MFS is defined as the time from randomisation until the date of first appearance of distant metastases, confirmed by standard clinical imaging [computed tomography (CT)/ magnetic resonance imaging (MRI) and bone scan, or prostate-specific membrane antigen-positron emission tomography (PSMA-PET)], as assessed by blinded independent central review (BICR) or death due to any cause.

Secondary endpoints 10

1. OS is defined as the time from randomisation until the date of death due to any cause.
2. MFS is defined as the time from randomisation until the date of distant metastases, confirmed by conventional imaging (CT/MRI and bone scan), or death due to any cause.
3. MFS is defined as the time from randomisation until the date of distant metastases, confirmed by PSMA-PET imaging or death due to any cause.
4. MFS is defined as the time from randomisation until the date of distant metastases, confirmed by standard clinical imaging (CT/MRI and bone scan or PSMA-PET), histology, or death due to any cause.
5. Time from randomisation to PFS2 is defined as the time from randomisation to the earliest of progression [defined as radiographic progression, clinical progression, or prostate-specific antigen (PSA) progression] after initiation of first subsequent systemic treatment following the initial investigator-assessed progression or death. The date of second progression will be investigator assessed according to local standard clinical practice.
6. Time to biochemical recurrence is defined as the time from randomisation to biochemical recurrence per Phoenix criteria.
7. PCSS is defined as the time from randomisation until the date of death due to the underlying prostate cancer.
8. TTDUS is defined as the time from randomisation to deterioration in EORTC-QLQ-PR25 (US) subscale scores.
9. TTDPF is defined as the time from randomisation to deterioration in EORTC-QLQ-C30 Physical Function subscale scores
10. To assess the PK of saruparib in plasma either with or without abiraterone and explore the relationship between the PK concentration/parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

11 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 107 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications