Arvinas will prioritize the initiation of phase 3 clinical trials of ARV-766 for the treatment of mCRPC

       Recently, Arvinas (ARVN.US) announced its androgen receptor (AR)-targeted PROTAC protein degrader bavdegalutamide (ARV-110) and its second-generation AR-targeted PROTAC degrader at the European Society for Medical Oncology (ESMO) Positive efficacy, tolerability results from a Phase 1/2 clinical trial of ARV-766 in patients with metastatic castration-resistant prostate cancer (mCRPC). Based on this data, Arvinas will prioritize the launch of a Phase 3 clinical trial of ARV-766 for the treatment of mCRPC and is scheduled to have relevant discussions with regulatory authorities in the second quarter of 2024. 

        It is understood that ARV-110 is a once-daily, oral AR-targeted PROTAC degrader that can degrade wild-type and all clinically relevant AR ligand-binding domain (LBD) mutations except the AR L702H mutation. ARV-766 is an improved, potential "first-in-class" and "best-in-class" drug that can simultaneously degrade AR L702H's PROTAC degrader.

       According to the extended follow-up data of the phase 1/2 clinical trial of ARV-110, when the AR L702H mutation is present in different tumors of the patients, a subgroup of mCRPC patients carrying the AR T878X/H878Y mutation (AR 878/875; T878X=T878A or T878S) The radiographic progression-free survival (rPFS) was 11.1 months, with 54% of patients having a ≥50% reduction in prostate-specific antigen (PSA) levels (PSA50).

       On the other hand, new data from the ongoing Phase 1/2 clinical trials of ARV-766 show that the drug exhibits outstanding efficacy and tolerability characteristics. ARV-766 achieved PSA50 in 41% of patients with mCRPC harboring any LBD mutation and in 50% of patients with mCRPC whose tumors harbored the AR L702H mutation. In addition, ARV-766 also showed better tolerability data than ARV-110. PFS data from this trial are expected to be available in 2024.