PETRANHA: Phase 1/2 study of AZD5305 + novel hormonal agents in patients with metastatic prostate cancer–Interim safety and pharmacokinetic results.

• DOI: 10.1200/jco.2024.42.4_suppl.123
• Publication Date: 2024-01-29T21:06:41Z
• Authors: Arun Azad; Mark Voskoboynik; Anthony M. Joshua; Andrew James Weic...; Peter Sankey; Simon Pacey; Elisabeth I. Heath; Laurence Krieger; Lisa Horvath; Patrick Glen Pilié; Lynsey Womersley; Spiros Linardopoulos; Ganesh Moorthy; TJ Zhou; Jessica Brown; Bruno de Paula; Edit Lukacs; Andrew Hudson
• Keywords: Interim; Interim analysis; Hormonal Therapy

123 Background: The combination of PARP inhibitors (PARPi) with novel hormonal agents (NHAs) has recently demonstrated significant improvement in progression-free survival patients (pts) metastatic castration-resistant prostate cancer (mCRPC) compared NHAs alone. AZD5305, a PARP1-selective inhibitor, the potential for an improved safety profile and limited drug-drug interactions (DDIs) first-generation PARPi. PETRANHA, open-label nonrandomized study, is evaluating DDIs AZD5305 physician’s choice NHA (enzalutamide [enza], abiraterone acetate [abi] or darolutamide [daro]) pts cancer. Methods: Pts were aged ≥18 years histologically confirmed mCRPC castration-sensitive (mCSPC), suitable treatment, without HRR mutations tumor tissue. Key exclusion criteria previous PARPi, platinum chemotherapy, targeted radioligand therapy mCSPC; docetaxel mCSPC. assigned to receive 60 mg once daily (OD; first dose level tested) either enza 160 OD (Arm 1), abi 1000 + 5 prednisone 2), daro 600mg twice 3) until disease progression any intolerable adverse event (AE) occurred. Primary objectives tolerability. evaluated each combination. Results: At data cutoff (July 10, 2023), 48 included interim analysis 1, n=11; Arm 2, n=19; 3, n=18). In total, 32 (66.7%) had mCRPC, 16 (33.3%) mCSPC, 8 (16.7%) pre-exposed NHAs. Median duration exposure was 6.3 months (range, 1.05–12.58) across all arms. Safety are presented Table. most common AEs anemia (52.1%; Gr ≥3, 16.7%), fatigue (50.0%; 2.1%), neutropenia (33.3%; 6.3%). No dose-limiting toxicities AE-related deaths occurred arm; leading discontinuations uncommon. clinically measured combinations. Conclusions: Initial safety, tolerability, DDI from PETRANHA study indicates that can be safely combined three individual low rates interruptions reductions. ongoing Australia, Italy, UK, USA. Clinical trial information: NCT05367440 . [Table: see text]