Safety And Efficacy Of The Bruton Tyrosine Kinase Inhibitor Zanubrutinib (Bgb-3111) In Patients With Waldenstrc6m Macroglobulinemia From A Phase 2 Trial

Background: The Bruton tyrosine kinase (BTK) inhibitor zanubrutinib has demonstrated greater selectivity for BTK versus other TEC- and EGFRfamily kinases in biochemical assays, and favorable pharmacokinetic/pharmacodynamic properties in preclinical studies. In a phase 1 clinical trial, zanubrutinib showed complete and sustained 24-hour BTK occupancy in both peripheral blood mononuclear cells and lymph node biopsies from patients treated with 160 mg twice daily (Tam et al. Blood 2016;128:642). Zanubrutinib was also associated with high and durable responses in patients with WaldenstrC6m macroglobulinemia (WM) (Tam, ASCO 2020, abstract 8007; Dimopoulos, EHA 2019, abstract PF487; Trotman, EHA 2019, abstract PF481). Here we present initial safety and efficacy data from a phase 2 trial of zanubrutinib in patients with relapsed or refractory (R/R) WM.