PK and PD Assessment of BET Inhibitor Pelabresib (CPI-0610) in Patients with Relapsed or Refractory Lymphoma: Findings from a Phase 1 Study

Background: Nuclear factor-κB (NF-κB), a transcription factor essential for inflammatory responses, is constitutively activated in many lymphomas. Pelabresib (CPI-0610) is a first-in-class, oral, small-molecule inhibitor of the tandem amino-terminal bromodomains (BD1 and BD2) of bromodomain and extraterminal domain (BET) proteins, which regulate gene expression pathways. In preclinical studies, pelabresib downregulated NF-κB signaling and demonstrated antitumor activity in vitro. Here we report the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability, and preliminary efficacy results from the first-in-human Phase 1, multicenter, open-label, dose-escalation study of pelabresib in patients (pts) with relapsed or refractory lymphomas (NCT01949883).