Bavdegalutamide Shows Mutation-Dependent Activity in Phase I/II Metastatic Prostate Cancer Study

A phase I/II study published in the Journal of Clinical Oncology evaluated oral bavdegalutamide (ARV-110), a proteolysis-targeting chimera androgen receptor (AR) degrader, in adult men with metastatic castration-resistant prostate cancer previously treated with an AR pathway inhibitor. Phase I enrolled 95 patients and established 420 mg once daily as the recommended phase II dose. Phase II enrolled 144 patients and assessed PSA responses and radiographic progression-free survival (rPFS) across molecularly defined and less-pretreated subgroups.

Among patients with AR T878 and/or H875 mutations (n=20), 60.0% achieved a PSA decline of at least 50%, and median rPFS was 11.1 months. Corresponding results were 4.3% and 4.2 months for wild-type AR or other alterations (n=46), and 3.1% and 5.1 months for AR L702H mutations or AR splice variant 7 expression (n=32). Among less-pretreated patients receiving one prior AR pathway inhibitor without prior chemotherapy (n=42), the PSA response rate was 21.4% and median rPFS was 11.1 months.

In phase II, grade 1/2 and grade 3 treatment-related adverse events occurred in 72.3% and 17.4%, respectively; none were grade 4 or higher. Treatment-related adverse events prompted dose reductions in 11.8% and discontinuation in 11.1%. These early findings suggest activity concentrated in specific AR-mutated tumors, but small subgroups, surrogate endpoints, and the absence of a reported comparator limit conclusions about clinical benefit. Full text was unavailable for assessment.