Arvinas Announces Detailed Results of Androgen Receptor PROTAC Protein Degrader

Today, Arvinas announced updated results from Phase 1 and Phase 2 clinical trials of its androgen receptor (AR)-targeting PROTAC protein degrader, bavdegalutamide (ARV-110)

Bavdegalutamide is an AR-targeting PROTAC protein degrader that recruits E3 ubiquitin ligases to the vicinity of ARs, tags ARs with ubiquitin, and guides them for proteasomal degradation

The latest trial results showed that bavdegalutamide reduced prostate-specific antigen (PSA) levels by ≥50% (PSA50) in 46% of all patients with AR T878X/H875Y mutations in phase 1 and 2 clinical trials

Image source: Arvinas official website

Furthermore, among patients with the AR T878X/H875Y mutation, 6 of 7 patients whose tumors could be assessed for clinical response using RECIST experienced tumor shrinkage, including two with confirmed partial responses

Image source: Arvinas official website

Arvinas said that more than 10% of mCRPC patients carry AR T878X/H875Y mutations, and blood-based circulating tumor DNA (ctDNA) testing can identify these patients and use bavdegalutamide to precisely treat them

In terms of safety, bavdegalutamide showed a manageable tolerability profile at the recommended dose in phase 2 clinical trials

Arvinas plans to initiate discussions with the US FDA to explore the potential of bavdegalutamide to treat patients with molecularly defined mCRPC through the accelerated approval pathway

References:

[1] Arvinas PROTAC® Protein Degrader Bavdegalutamide (ARV-110) Continues to Demonstrate Clinical Benefit in Men with Metastatic Castration-Resistant Prostate Cancer.

[2] Bavdegalutamide (ARV-110): Phase 1 Dose Escalation and Interim ARDENT Phase 2 Dose Expansion Trial Results.