Saruparib in Combination with Physician’s Choice of ARPI in Patients with mHSPC Previously Treated with Docetaxel or 177Lu-PSMA Therapy without Disease Progression and PSA ≥ 0.2 ng/mL (EvoPAR-PR05) - EvoPAR-PR05

Inclusion Criteria

• Inclusion Criteria:
• - Participant must be ≥ 18 at the time of signing the informed consent.
• - Histologically documented diagnosis of prostate adenocarcinoma that is de novo or recurrent and hormone-sensitive.
• - Metastatic disease confirmed prior to initiation of previous treatment with docetaxel or Lu-PSMA-containing regimens for mHSPC.
• - Previous treatment with docetaxel (IV, Q3w)- or Lu-PSMA (IV, Q6w) with last dose within past 6 months.
• - Participants must have the following:
• • Must be receiving ADT with a GnRH analogue or has undergone bilateral orchiectomy.
• • Had no evidence of disease progression
• • Had all toxicities related to docetaxel- or Lu-PSMA-containing treatment (except for alopecia and peripheral neuropathy) resolved to CTCAE Grade 1 or lower.
• - PSA ≥ 0.2 ng/mL within 14 days prior to randomization.
• - Serum testosterone < 1.7 nmol/L or 50 ng/dL.
• - Palliative radiotherapy for symptoms management will be permitted and is to be completed at least 4 weeks prior to randomization for wide field radiation therapy and at least 2 weeks prior to randomization for limited field radiation therapy.
• - Provision of a FFPE tumor tissue sample and a blood sample (for ctDNA).
• - Confirmed HRRm, HRD and PTEN status.
• - Adequate organ and bone marrow function.
• - Minimum life expectancy of 6 months.
• - Male, assigned at birth, inclusive of all gender identities.
• - Contraceptive use by participants or participant partners should be consistent with local regulations.
• - Capable of giving signed informed consent.
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• Exclusion Criteria:
• - Hypersensitivity to saruparib, ARPI or any excipients of these products or any contraindication or restriction based on the local label.
• - Any history of persisting (> 2 weeks) severe cytopenia due to any cause (eg, ANC< 0.5 × 10^9/L or platelets < 50 × 10^9/L)
• - Any known predisposition to bleeding (eg, active peptic ulceration, recent [within6 months] hemorrhagic stroke, proliferative diabetic retinopathy.
• - Spinal cord compression or brain metastases unless asymptomatic and stable.
• - History of MDS/AML or with features suggestive of MDS/AML
• - History of another primary malignancy, with some exceptions.
• - Any chronic gastrointestinal diseases or conditions including inability to swallow the formulated product that would preclude adequate absorption of any study drug.
• - History of seizure or predispose to seizure, including any history of loss of consciousness or transient ischemic attack within 12 months of enrolment.
• - Serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
• - Major surgical procedure or significant traumatic injury within 4 weeks of the first dose or an anticipated need for major surgery during the study.
• - Switched ARPI agent in previous treatment for mHSPC due to disease progression. Note: if the ARPI agent was switched due to any reason other than disease progression and switch was prior to ICF signature, participants will be eligible.
• - Any prior treatment with a PARPi or platinum chemotherapy.
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