Phase III, randomized, double-blind, placebo-controlled study of adjuvant saruparib (AZD5305) in patients with BRCAm localized high-risk prostate cancer who are receiving radiotherapy and androgen deprivation therapy (EvoPAR-Prostate02).

TPS412 Background: PARP inhibitors (PARPi) are approved for the treatment of patients with metastatic castration-resistant prostate cancer. Saruparib is a new generation PARPi that selectively inhibits and traps PARP1. In the Phase I/IIa PETRA study (NCT04644068), activity with saruparib monotherapy (PSA 50 , objective response) has been observed in patients with advanced/metastatic prostate cancer. The Phase I/II PETRANHA study (NCT05367440) has demonstrated that saruparib can be safely combined with androgen receptor pathway inhibitors to treat patients with metastatic prostate cancer. The Phase III EvoPAR-Prostate02 study (NCT06952803) is evaluating the efficacy and safety of adjuvant saruparib versus placebo in patients with early-stage, high-risk prostate cancer with BRCA1 / BRCA2 gene mutation (BRCAm) who have received definitive radiotherapy (RT) and are receiving a standard concomitant androgen deprivation therapy (ADT) regimen. Methods: EvoPAR-Prostate02 is a two-cohort, randomized, double-blind, placebo-controlled study. Eligibility criteria include age ≥18 years, diagnosis of high-risk or very high-risk localized/locally advanced prostate adenocarcinoma or high-risk biochemical recurrence following radical prostatectomy, with a confirmed BRCAm by central tumor tissue testing. Patients must have completed primary or salvage RT with curative intent, with no evidence of disease or disease detected only in the pelvis at time of study entry, and must still be receiving ADT. Key exclusion criteria include persistent cytopenias, conditions with predisposition to bleeding, and history of myelodysplastic syndrome/acute myeloid leukemia. In both Cohort A (ADT alone) and Cohort B (ADT plus abiraterone/prednisone), randomization is 1:1 to saruparib or placebo. Treatment with saruparib/placebo continues for 24 months or until unacceptable toxicity, confirmed disease progression by blinded independent central review (BICR), or patient-initiated withdrawal. ADT and abiraterone treatment duration is limited to 24 months, inclusive of pre-study regimen. The primary endpoint is metastasis-free survival (MFS), confirmed by standard clinical imaging (computed tomography/magnetic resonance imaging and bone scan, or prostate-specific membrane antigen-positron emission tomography PSMA PET), as assessed by BICR. Overall survival (OS) is a key secondary endpoint. Statistical analyses of MFS and OS will be conducted within each cohort using a stratified log-rank test. Approximately 700 patients will be randomized. Recruitment began in July 2025 and is ongoing. Clinical trial information: NCT06952803 .