Luxdegalutamide — Investigational Agent
Androgen Receptor Degrader · Phase 2 · Novartis (acquired from Arvinas)
Mechanism of Action
Luxdegalutamide is an oral PROTAC (proteolysis-targeting chimera) androgen receptor degrader. It bifunctionally binds both the AR ligand-binding domain and an E3 ubiquitin ligase (cereblon), tagging AR for polyubiquitination and proteasomal degradation rather than simply antagonizing it. By eliminating the AR protein—including clinically relevant ligand-binding-domain mutants (e.g., L702H, H875Y, T878A) that drive resistance to enzalutamide and abiraterone—it overcomes signaling that persists with conventional AR antagonists. This degradation strategy addresses tumors that have escaped…
Investigational Indications
- Metastatic castration-resistant prostate cancer with AR ligand-binding domain mutations
- ARPI-pretreated mCRPC