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

Inclusion 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.

Exclusion Criteria

• 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.