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

Abstract

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-naïve 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.

• Authors: Constantine S Tam, Hang Quach, Andrew Nicol, Xavier Badoux, Hannah Rose, H Miles Prince, Michael F Leahy, Richard Eek, Nicholas Wickham, Sushrut S Patil, Jane Huang, Radha Prathikanti, Aileen Cohen, Rebecca Elstrom, William Reed, Jingjing Schneider, Ian W Flinn
• Journal: Blood advances (Blood Adv) Vol. 4 Issue 19 Pg. 4802-4811 (10 13 2020) ISSN: 2473-9537 [Electronic] United States
• PMID: 33022066 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Piperidines
• Pyrazoles
• Pyrimidines
• zanubrutinib
• obinutuzumab

Topics

• Antibodies, Monoclonal, Humanized
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy)
• Lymphoma, Follicular
• Piperidines
• Pyrazoles
• Pyrimidines (adverse effects)