Phase 1/2 PETRANHA Trial Update: Promising Results Reported at ESMO 2025

At the 2025 ESMO Congress, new data from the phase 1/2 PETRANHA trial introduced saruparib (AZD5305), a highly selective PARP1 inhibitor, as a potentially safer and more effective therapeutic partner for androgen receptor pathway inhibitors (ARPIs) in metastatic prostate cancer. The results highlighted a strong efficacy signal in castration-sensitive disease and ARPI-naïve castration-resistant settings, while maintaining manageable safety across treatment groups.​

Unlike earlier broad-spectrum PARP inhibitors that target both PARP1 and PARP2, saruparib’s selectivity aims to retain synthetic lethality in tumor cells while minimizing myelosuppressive side effects. The phase 1/2 PETRANHA study tested this compound at 60 mg daily in combination with enzalutamide, abiraterone, or darolutamide in 77 patients divided among metastatic castration-sensitive (mCSPC) and metastatic castration-resistant (mCRPC) cohorts.​

Patients with metastatic castration-sensitive disease achieved an objective response rate (ORR) of 88.5%, with complete PSA reductions in all patients and undetectable levels in 83%. Among ARPI-naïve mCRPC patients, the ORR reached 73.3%, compared with 25% in those who had received prior ARPI therapy. Importantly, PSA declines and radiographic responses were seen in both HRR-mutated and wild-type tumors, underscoring that saruparib’s benefit may extend beyond traditional biomarker-defined populations.​

The treatment demonstrated a favorable safety balance. Adverse events occurred in nearly all patients, though most were grade 1–2. Rates of grade ≥3 events ranged between 32% and 52%, consistent with other PARP combination regimens. Median saruparib exposure extended beyond a year in mCSPC patients, reflecting favorable durability and adherence.​

With these findings, saruparib advances into phase 3 development through the EvoPAR‑Prostate01 study. This global, double-blind, placebo-controlled trial is enrolling up to 1,800 participants with metastatic castration-sensitive prostate cancer, both with and without HRR mutations. All patients will receive physician’s choice of ARPI (abiraterone, enzalutamide, or darolutamide) with the addition of saruparib or placebo. The primary outcome is radiographic progression-free survival, supported by key secondary endpoints including overall survival and skeletal event–free survival.​

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