Saruparib (AZD5305) vs Placebo in Men With Metastatic Castration-Sensitive Prostate Cancer Receiving Physician's Choice New Hormonal Agents

Eligibility Criteria

• * Male ≥ 18 years of age.
• * Histologically documented prostate adenocarcinoma which is de novo or recurrent and castration-sensitive. Participants with pathologic features of small cell, neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are not eligible.
• * Metastatic disease as documented by the investigator prior to randomisation, with clear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion that is suitable for repeated assessment with CT and/or MRI.
• * Participant is receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy starting ≥ 14 days and \< 4 months prior to randomisation.
• * ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to randomisation.
• * Provision of FFPE tumour tissue sample and blood sample (for ctDNA).
• * Confirmed HRRm status by central tumour tissue and/or ctDNA test is required to determine cohort eligibility.
• * Adequate organ and bone marrow function as described in study protocol.
• * Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention.
• * Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.
• * Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). In case there is no clinical MDS/AML suspicion, no specific screening for MDS/AML (by BM/bone biopsy) is required.
• * Participants with any known predisposition to bleeding.
• * Any history of persisting (\> 2 weeks) severe cytopenia.
• * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 and/or the assigned NHA.
• * History of another primary malignancy, with exceptions.
• * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy.
• * Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
• * Cardiac criteria, including history of arrhythmia and cardiovascular disease.
• * Any prior anticancer pharmacotherapy or surgery for metastatic prostate cancer, with exceptions.
• * Prior treatment within 14 days with blood product support or growth factor support.
• * Participants who are unevaluable for both bone and soft tissue progression.