The phase III TALAPRO-2 study aims to demonstrate the combination of the PARP inhibitor talazoparib plus androgen receptor-targeted therapy, enzalutamide for metastatic castration-resistant prostate cancer. The design of the much-anticipated trial was recently published in the journal Future Oncology.
The current standard of care treatment for metastatic castration-resistant prostate cancer (mCRPC) includes therapies such as enzalutamide or abiraterone that target the androgen receptor. A significant number (23-27%) of men that enroll have mutations in genes involved in DNA damage repair (DDR), such as BRCA1/2 ATM. The PARP inhibitors have shown efficacy as monotherapy in tumour cells with DDR and are expected to increase sensitivity to AR therapies. Previously, a proof-of-concept study combining olaparib (PARPi) plus abiraterone (AR therapy) showed improvement in median progression-free survival (PFS).
TALAPRO-2 is a multinational, phase III, randomised (1:1), double-blind, placebo-controlled study comparing the efficacy and safety of talazoparib (0.5 mg/day, oral) plus enzalutamide (160 mg/day) versus enzalutamide alone in patients with mCRPC with or without DDR alterations. The study aims to enroll 1,037 patients with eligibility criteria including age ≥18 years, asymptomatic/mildly symptomatic mCRPC, ECOG performance status ≤1, metastatic disease. The primary co-endpoints of the study include radiographic PFS in all patients and patients with alterations in DDR genes. The study’s secondary endpoints include overall survival and incidences of adverse events.
Taken together, the TALAPRO-2 study will be able to show if combining PARPi with AR-therapy will be able to prolong radiographic PFS in selected mCRPC (alterations in DDR) or un-selected patients.