Arvinas presents interim data from Phase 1/2 clinical trial for bavdegalutamide

Arvinas announced the presentation of interim data from the company’s Phase 1/2 clinical trial for bavdegalutamide, a novel PROTAC protein degrader targeting the androgen receptor, in a poster session at the European Society for Medical Oncology Congress being held in Madrid from October 20 – 24, 2023. The company will host a conference call to discuss these data and present new data from an updated analysis of its ongoing Phase 1/2 clinical trial with its second-generation PROTAC AR degrader, ARV-766, showing clinical activity extending across patients harboring tumors with AR LBD mutations and a tolerability profile that is superior to bavdegalutamide. Extended follow-up of data from the Phase 1/2 clinical trial with bavdegalutamide showed radiographic progression free survival of 11.1 months in a subgroup of patients with metastatic castration-resistant prostate cancer and tumors harboring AR T878X/H878Y mutations in the absence of co-occurring AR L702H mutations. AR L702H is a common AR ligand-binding domain mutation that is not potently degraded by bavdegalutamide. In patients with tumors harboring any AR LBD mutation except L702H alone, bavdegalutamide showed an rPFS of 8.2 months. Bavdegalutamide is a once-daily, oral, first-in-class PROTAC AR degrader that degrades wild type and all clinically relevant AR LBD mutations except AR L702H. ARV-766 was designed to improve upon the degradation profile of bavdegalutamide by also degrading AR L702H. The prevalence of all AR LBD mutations, especially AR L702H, has increased over time, and these mutations are present in approximately 25% of tumors after initial treatment with a novel hormonal agent such as enzalutamide or abiraterone. This represents a potential addressable patient population for ARV-766 that is approximately three times that of bavdegalutamide in the post-NHA population due to its broader degradation profile. New data from the ongoing Phase 1/2 clinical trial of ARV-766 continues to show robust efficacy in tumors with all LBD mutations and in patients with tumors harboring AR L702H mutations. In addition to a tolerability profile that is superior to bavdegalutamide, early durability data for ARV-766 are encouraging and provide additional support for prioritizing ARV-766 over bavdegalutamide, with PFS data anticipated in 2024.