AUA 2024: EvoPAR-Prostate01: Phase III, Double-Blind, Placebo-Controlled, 2-Cohort, Randomized Study of Saruparib (AZD5305) in Combination with New Hormonal Agents in Patients with mCSPC +/- HRR Mutations
(UroToday.com) The 2024 American Urological Association (AUA) annual meeting featured a session on prostate cancer trials in progress, and a presentation by Dr. Neeraj Agarwal discussing EvoPAR-Prostate01, a phase III, double-blind, placebo-controlled, 2-cohort, randomized study of saruparib (AZD5305) in combination with new hormonal agents in patients with metastatic castration-sensitive prostate cancer (mCSPC) with and without homologous recombination repair (HRR) mutations. ADT plus new hormonal agents have improved outcomes for patients with mCSPC, but patients will eventually progress to mCRPC, which is associated with poor survival outcomes. As such, there is a need for effective treatments in mCSPC that can delay initiation of chemotherapy and progression to mCRPC. Combinations of PARP inhibitor plus new hormonal agents have demonstrated clinical benefit in patients with mCRPC [1-3]. In other indications, the clinical activity of PARP inhibitors in earlier lines of treatment has demonstrated potential to provide greater magnitude of benefit and delay disease progression. Of note, the efficacy and safety of PARP inhibitor therapy for patients with HRR mutated mCSPC are being assessed in the ongoing phase III studies TALAPRO-3 and AMPLITUDE.
Saruparib (AZD5305), a first-in-class PARP1 inhibitor, was developed through rational design to be highly selective for PARP1, with increased potency and improved physicochemical properties versus other approved PARP inhibitors. In the PETRA study (NCT04644068), the favorable safety profile and low dose-reduction rate observed with saruparib monotherapy compared with approved PARP inhibitors suggest that patients may be able to remain on treatment longer at an optimal dose (60 mg QD), which may improve efficacy. The safety and efficacy of saruparib plus new hormonal agents for the treatment of mCSPC and mCRPC are being assessed in the Phase I/IIa PETRANHA study (NCT05367440), with the initial data indicated that saruparib (60 mg QD) can be safely combined with enzalutamide, abiraterone acetate, or darolutamide. Low rates of hematologic and gastrointestinal toxicities, as well as low rates of dose reductions or discontinuations, were observed.
EvoPAR-Prostate01 will assess a mCSPC patient’s HRR mutation biomarker status, at which time they will enter the HRR mutation (~550 patients) or the non-HRR mutation (~1,250) cohort of the trial, followed by randomization 1:1 to either saruparib 60 mg plus physician’s choice of new hormonal agent versus placebo plus physician’s choice of new hormonal agent. The trial design is as follows:
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