Saruparib + androgen receptor pathway inhibitor (ARPI) + androgen deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC): The phase 1/2 PETRANHA trial.

Abstract

177 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) + ARPI + ADT have improved clinical outcomes versus ARPI + ADT alone in pts with metastatic castration-resistant prostate cancer (mCRPC), particularly those with BRCA mutations. Interim efficacy results from the Phase 1/2 PETRANHA study (NCT05367440) showed high rates of undetectable prostate specific antigen (uPSA) levels in pts with mHSPC who received saruparib, a PARP1 selective inhibitor, + ARPI + ADT, irrespective of homologous recombination repair mutation (HRRm) status (Azad A, et al. ESMO 2025 [2384MO]). We report updated efficacy and safety results for pts with mHSPC. Methods: Pts received oral saruparib 60 mg once daily + physician’s choice of ARPI (enzalutamide, abiraterone acetate or darolutamide) + ADT. ADT for up to 6 months prior to consent was permitted. Prior chemotherapy for metastatic prostate cancer was not allowed. Treatment continued until disease progression or intolerable toxicity. Results: At data cutoff (June 10, 2025), 93 pts with mHSPC were treated with saruparib + ARPI (enzalutamide [n=3], abiraterone acetate [n=14] or darolutamide [n=76]) + ADT, with a median follow-up of 16.4 months (min–max, 0.0–34.8). Overall, 55.9% (52/93) of pts had high volume disease, 12.9% (12/93) had visceral metastasis, and the baseline median PSA level was 2.5 ng/mL. In response evaluable pts (34/93), the objective response rate (ORR) was 82.4% (28/34; 80% CI, 71.1–90.5), including 5 complete responses (14.7%). The confirmed uPSA rate at any time was 69.9% (65/93; 80% CI, 63.0–76.1) and confirmed 52-week uPSA rate was 76.7% (46/60; 80% CI, 68.2–83.7). For pts with HRRm versus non-HRRm, ORR was 100% (4/4) and 85.7% (12/14); confirmed uPSA rate at any time was 71.4% (10/14) and 70.6% (24/34); and confirmed 52-week uPSA rate was 77.8% (7/9) and 73.9% (17/23), respectively. The combination had a manageable safety profile (Table). Conclusions: In pts with mHSPC, saruparib + ARPI + ADT induced high ORRs and high 52-week uPSA rates. Efficacy was observed regardless of HRRm status. The safety profile of the combination was manageable with no new safety signals. These findings warrant confirmation in the ongoing Phase 3 EvoPAR-Prostate01 trial. Clinical trial information: NCT05367440 . Safety summary (N=93). Median total duration of saruparib / ARPI exposure, months (min–max) 16.3 (0.7–35.6) / 16.5 (0.7–35.6) Safety parameter, n (%) Any AECausally related to saruparib 92 (98.9)83 (89.2) Any Grade ≥3 AECausally related to saruparib 45 (48.4)29 (31.2) Any serious AECausally related to saruparib 24 (25.8)8 (8.6) Saruparib / ARPI discontinuation due to AE* 7 (7.5) / 3 (3.2) Saruparib / ARPI dose reduction due to AE* 24 (25.8) / 3 (3.2) Saruparib / ARPI interruption due to AE* 52 (55.9) / 36 (38.7) *Irrespective of the action taken on other drugs. AE, adverse event.