Enzalutamide Plus Venetoclax Shows Early Signals of Activity in mCRPC

In this phase Ib trial for metastatic castration-resistant prostate cancer, enzalutamide was combined with escalating doses of venetoclax (up to 800 mg/day) in a 3+3 design with no dose-limiting toxicities observed; despite sub-therapeutic venetoclax plasma levels, the regimen produced acceptable safety, modest PSA50 responses in 10% of patients, and disease stabilization in 40%, alongside pharmacodynamic evidence of BCL-2 modulation.

The findings suggest that even with lower-than-target venetoclax exposure, the drug combination effectively impacts BCL-2 regulation and warrants further exploration as a potential strategy to overcome resistance in mCRPC.