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 andcastration-sensitive. Participants with pathologic features of small cell,neuroendocrine, sarcomatoid, spindle cell, or signet cell histology are noteligible.

• Metastatic disease as documented by the investigator prior to randomisation, withclear evidence of ≥ 1 bone lesion and/or ≥ 1 soft tissue lesion that is suitable forrepeated assessment with CT and/or MRI.

• Participant is receiving ADT with a GnRH analogue or has undergone bilateralorchiectomy starting ≥ 14 days and < 4 months prior to randomisation.

• ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior torandomisation.

• Provision of FFPE tumour tissue sample and blood sample (for ctDNA).

• Confirmed HRRm status by central tumour tissue and/or ctDNA test is required todetermine 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 thestudy 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 (asdetermined by prior diagnostic investigation). In case there is no clinical MDS/AMLsuspicion, 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 toswallow the formulated product or previous significant bowel resection that wouldpreclude 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 notrequiring 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, withexceptions.

• Prior treatment within 14 days with blood product support or growth factor support.

• Participants who are unevaluable for both bone and soft tissue progression.