Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory (R/R) Indolent NHL: Results from the Phase 1 CaDAnCe-101 Study

Abstract

Introduction: Bruton tyrosine kinase (BTK) inhibitors have significantly advanced the treatment of patients with B-cell malignancies. However, disease progression can still occur, sometimes due to BTK mutations, necessitating the development of therapies that can inhibit BTK-mediated signaling via an alternative mechanism. BGB-16673 is a bivalent small molecule that induces BTK degradation by binding specifically to BTK and the E3 ligase. The E3 ligase catalyzes the transfer of ubiquitin molecules to BTK which marks BTK for destruction by the proteasome. In preclinical models, BGB-16673 degraded wild-type and mutant forms of BTK associated with resistance to covalent (cBTKi) and noncovalent ..