Saruparib added to hormone-blocking therapy for metastatic hormone-sensitive prostate cancer

Who can take part

• 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
• - -

Who cannot take part

• 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
• Hypersensitivity to saruparib, ARPI or any excipients of these products or any contraindication or restriction based on the local label
• Any known predisposition to bleeding (eg, active peptic ulceration, recent [within6 months] hemorrhagic stroke, proliferative diabetic retinopathy
• 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
• 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)
• Spinal cord compression or brain metastases unless asymptomatic and stable
• - -