Phase 1/2a study of AZD5305, a novel poly(adenosine diphosphate ribose) polymerase (PARP) 1-selective inhibitor in combination with new hormonal agents (NHAs) in patients (pts) with metastatic prostate cancer (mPC).

• DOI: 10.1200/jco.2023.41.6_suppl.tps296
• Publication Date: 2023-03-14T15:22:32Z
• Authors: Arun Azad; Mark Voskoboynik; Ana Filipa Palma ...; Anthony M. Joshua; Andrew James Weic...; Robert J. Jones; Pasquale Rescigno; Ben Tran; Caroline Kennedy; Spiros Linardopoulos; Ganesh Moorthy; TJ Zhou; Jessica S Brown; Edit Lukacs; Richard Francis; Andrew Hudson
• Keywords: Olaparib; PARP inhibitor; PARP1; Enzalutamide

TPS296 Background: AZD5305 is a potent and selective oral PARP inhibitor (PARPi) that specifically targets traps PARP1, in contrast to approved PARPis which target both PARP1 PARP2. Preclinical data suggest inhibition confers antiproliferative effects, while PARP2 major driver of hematological toxicity. Thus, may have an improved therapeutic index with less The Phase 3 PROpel study showed first-line olaparib plus abiraterone (abi) significantly radiographic progression-free survival (rPFS) over abi alone pts metastatic castration-resistant prostate cancer (mCRPC) enrolled irrespective homologous recombination repair (HRR) gene mutations (Clarke et al, NEJM Evidence 2022). There need for better understanding the benefit adding PARPi NHA potential synergy between them early treatment mPC. PETRANHA (NCT05367440) evaluating combination physician’s choice including abi, darolutamide, enzalutamide, Methods: This multi-arm, open-label, nonrandomized dose-escalation phase study. Key eligibility criteria include age ≥18 years, histologically confirmed mPC (mCRPC or castration-sensitive [mCSPC], suitability treatment, ECOG PS 0–1, life expectancy ≥16 wks. HRR mutation status assessed at screening by testing blood, tumor circulating (ct) DNA; however, identified not required entry. exclusion mCRPC previous PARPi, platinum chemotherapy, targeted radioligand therapy. For mCSPC, key are same, docetaxel mCSPC setting. Treatment continues until disease progression, starting alternative anticancer therapy, unacceptable primary objectives assess safety tolerability NHAs, terms adverse events (AEs), serious AEs, dose-limiting toxicities. secondary characterization pharmacokinetics, changes size prostate-specific antigen level, assessment preliminary antitumor activity objective response rate, rPFS, time duration RECIST v1.1 Prostate Cancer Clinical Trials Working Group criteria. Exploratory endpoints role predictive biomarkers longitudinal ct cells ctDNA, membrane positron emission tomography (PET) fluorodeoxyglucose PET. Enrollment began on June 23, 2022, Melbourne, Australia; additional sites planned Australia, USA, Europe. trial information: NCT05367440 .