Ok, I am not so impressed with this new molecule, but here it is.
BMS-986365 is designed to inhibit androgen receptor (AR) activity through a dual mechanism of degrading the receptor and blocking its function, aiming to overcome resistance to standard AR pathway inhibitors like enzalutamide and abiraterone.
Over a median follow-up of 14.8 months, the therapy demonstrated a manageable safety profile with no grade 4 or higher treatment-related adverse events or discontinuations.
Efficacy results showed dose-dependent reductions in prostate-specific antigen (PSA) levels. At the highest dose of 900 mg twice daily, 70% of patients achieved at least a 30% reduction in PSA levels, and 50% achieved a 50% reduction. The median radiographic progression-free survival (rPFS) was 6.3 months overall, with a notable difference between patients who were chemotherapy-naïve (16.5 months rPFS) and those previously treated with chemotherapy (5.5 months rPFS).
Importantly, clinical benefits were observed regardless of AR ligand binding domain mutation status, suggesting that BMS-986365 could be effective across a broad spectrum of mCRPC patients. These findings highlight the potential of BMS-986365 as a first-in-class therapy capable of overcoming resistance to existing AR inhibitors.
