High overall response rate with the BTK inhibitor BGB-3111 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: An update on safety and activity.

Introduction: BGB-3111 is a potent, highly specific, and irreversible Bruton tyrosine kinase (BTK) inhibitor, with greater selectivity for BTK vs other TEC- and EGFR-family kinases and favorable pharmacokinetic and pharmacodynamic properties. BGB-3111 was shown to achieve complete, continuous BTK occupancy in peripheral blood mononuclear cells and lymph nodes and was associated with durable clinical responses in patients (pts) with CLL/SLL and Waldenstrom macroglobulinemia. Here, updated preliminary safety and activity data in relapsed/refractory (R/R) and treatment-naive (TN) pts with CLL/ SLL are reported. Method(s): This is an open-label, multicenter, phase 1b study of BGB-3111 in pts with B-cell malignancies. Pts with R/R CLL/SLL were included in dose escalation, and both TN and R/R CLL/SLL pts were included in expansion cohorts at the recommended phase 2 dose (320 mg/d, given once daily [QD] or split as a twice-daily [BID] dose). Adverse events (AEs) are reported per Common Terminology Criteria for AEs version 4.03, and response per the modified iwCLL criteria (Hallek 2008, Cheson 2012 clarification for novel therapies). Result(s): As of 15 Dec 2016, 68 pts with CLL/SLL (50 R/R and 18 TN) were enrolled: 4 pts in dose escalation and 64 in cohort expansion at doses of 160 mg QD (n = 3), 160 mg BID (n = 25), and 320 mg QD (n = 40). Patient characteristics are shown in Table 1. Safety: Median follow-up was 7.2 (range, 0-23.3) months. The most frequent AEs of any cause were bruising (35%) and petechiae (11%), upper respiratory tract infection (28%), fatigue (25%), cough (22%), and diarrhea (21%). Four serious AEs related to BGB-3111 were seen in 3 pts: grade (Gr) 2 cardiac failure, Gr 2 pleural effusion, Gr 3 purpura, and Gr 3 pneumonia. The case of Gr 3 purpura (subcutaneous hemorrhage) was the only major bleeding event reported. Atrial fibrillation (Gr 3) occurred in 1 pt. One pt discontinued BGB-3111 for an AE (pleural effusion). Activity: of the 54 pts evaluable