Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma

Zanubrutinib (BGB-3111) is a next-generation Bruton tyrosine kinase inhibitor designed to be more selective with fewer off-target effects. We conducted a phase 1 study to assess the safety of its combination with obinutuzumab and evaluate early efficacy in 81 patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or relapsed/refractory (R/R) follicular lymphoma (FL). In this phase 1b study, zanubrutinib was tolerable at 160 mg twice daily or 320 mg once daily combined with IV obinutuzumab in patients with CLL/SLL (n=45) and FL (n=36). Common adverse events (AEs) included upper respiratory tract infection (51%; n=23), neutropenia (44%; n=20), contusion (33%; n=15), cough, diarrhea, or fatigue (27%; n=12 each), and pyrexia (22%; n=10) in CLL/SLL patients and upper respiratory tract infection (39%; n=14), contusion (28%; n=10), fatigue (25%; n=9), and cough (22%; n=8) in FL patients. Neutropenia was the most common grade 3/4 AE (CLL/SLL, 31% [n=14]; FL, 14% [n=5]). Five patients required temporary dose reductions, and 5 discontinued the study drug because of AEs. Overall response rate (ORR) was 100% (n=20) in treatment-naive CLL patients and 92% (n=23) in R/R CLL patients. ORR in 36 R/R FL patients was 72% (n=26), with 14 complete and 12 partial responses. Median follow-up was 29 months (range, 8-37) for CLL patients and 20 months (range, 2-37) for FL patients. Zanubrutinib and obinutuzumab combination therapy was generally well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02569476.