AstraZeneca Continues Phase 1/2a PETRANHA Trial of Saruparib Combination for Prostate Cancer
Clinical Design and Current Status
The PETRANHA trial, sponsored by AstraZeneca (AZN) and supported by Bayer, is a multi-center, open-label, non-randomized Phase 1/2a study enrolling 174 patients with metastatic prostate cancer. Initiated in June 2022, the trial is currently Active, Not Recruiting, with a primary completion date expected on April 11, 2031. The trial primarily evaluates safety, serious adverse events, dose-limiting toxicity (DLT), pharmacokinetics (PK), and pharmacodynamics (PD), while also assessing early efficacy endpoints such as objective response rate (ORR), duration of response (DoR), and radiographic progression-free survival (rPFS) to refine the dosing and patient population for later-stage clinical development.
Drug and Combination Strategy
Saruparib, also known by its developmental name AZD5305, is a next-generation, oral, selective PARP1 inhibitor without a brand name. It captures PARP1, a protein involved in DNA damage repair, to induce cancer cell death. Unlike approved PARP inhibitors that inhibit both PARP1 and PARP2, saruparib's selective inhibition of PARP1 aims to reduce hematological toxicity and broaden the therapeutic window. The combination partners include the androgen receptor (AR) inhibitor Xtandi (enzalutamide), the CYP17A1 inhibitor Zytiga (abiraterone acetate) with prednisone, the AR inhibitor Nubeqa (darolutamide), and Erleada (apalutamide). The trial addresses both castration-sensitive and castration-resistant metastatic disease, combining hormonal pathway blockade with DNA repair inhibition.
Clinical Data and Development Significance
The 2025 interim analysis of Part A included 77 patients: 18 on saruparib 60mg once daily with enzalutamide, 23 with abiraterone and prednisone, and 36 with darolutamide. The apalutamide group was still enrolling and thus excluded from the analysis. The trial enrolls patients regardless of homologous recombination repair (HRR) mutation status to explore whether PARP1 selectivity can extend clinical benefit to non-mutant populations. Early safety and drug interaction data have already informed the Phase 3 EvoPAR-Prostate01 trial, positioning PETRANHA as more than a dose-finding study but as a foundational platform for building the saruparib prostate cancer franchise.
Competition, Regulatory, and Market Context
The U.S. FDA approved Lynparza (olaparib) in combination with abiraterone for BRCA-mutant metastatic castration-resistant prostate cancer (mCRPC) on May 31, 2023; Talzenna (talazoparib) with enzalutamide for HRR-mutant mCRPC on June 20, 2023; and Akeega (niraparib) in fixed combination with abiraterone for BRCA-mutant mCRPC on August 11, 2023. In addition to these PARP combination therapies, docetaxel, Pluvicto (lutetium Lu 177 vipivotide tetraxetan), and AR pathway inhibitors form the competitive treatment landscape. Saruparib must demonstrate its selectivity-based safety profile and broader patient applicability to stand out. The global prostate cancer treatment market is projected to grow from USD 17.0 billion in 2024 to USD 31.9 billion by 2030. If late-stage clinical trials confirm efficacy and reduced myelotoxicity, AstraZeneca could expand its Lynparza portfolio into next-generation PARP1 assets.
PETRANHA is validating the combination of saruparib with four androgen receptor pathway inhibitors in a 174-patient Phase 1/2a trial, with ongoing safety, drug interaction, and early efficacy tracking until the primary completion date of April 2031. The competitive landscape includes FDA-approved Phase 3 evidence-based therapies such as Lynparza with abiraterone, Talzenna with enzalutamide, Akeega, and Pluvicto. For saruparib to succeed, its PARP1 selectivity must translate into measurable improvements in anemia and thrombocytopenia, as well as better treatment persistence. As the global prostate cancer treatment market expands from USD 17.0 billion in 2024 to USD 31.9 billion by 2030, the ability to replicate clinical benefit in HRR non-mutant patients could significantly broaden its commercial potential. In the short term, the safety and response durability of PETRANHA combinations will determine Phase 3 execution risks, while in the medium to long term, it will influence AstraZeneca's next-generation PARP franchise evolution and the competitive positioning of Bayer and Astellas' hormonal agents in combination therapies.
Source: ClinicalTrials.gov (api_ct)