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)

A Randomized, Double-Blind, Placebo-Controlled, 2-Cohort, Phase III Study of Saruparib Combined With Physician's Choice of Androgen Receptor Pathway Inhibitor in Patients With Metastatic Hormone-Sensitive Prostate Cancer, Previously Treated With Docetaxel or PSMA-directed 177Lutetium-Containing Therapy Without Disease Progression, and With Prostate-Specific Antigen ≥ 0.2 ng/mL: EvoPAR-Prostate05

The primary objective of this study is to measure efficacy of saruparib + physician's choice of ARPI compared with placebo + ARPI in men with metastatic hormone-sensitive prostate cancer (mHSPC) who have previously received docetaxel chemotherapy or a prostate-specific membrane antigen (PSMA)-directed lutetium-177 radioligand therapy with no evidence of disease progression and PSA ≥ 0.2 ng/mL.

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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