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

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

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12 Citations (Web of Science)

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 5 45) and FL (n 5 36). Common adverse events (AEs) included upper respiratory tract infection (51%; n 5 23), neutropenia (44%; n 5 20), contusion (33%; n 5 15), cough, diarrhea, or fatigue (27%; n 5 12 each), and pyrexia (22%; n 5 10) in CLL/SLL patients and upper respiratory tract infection (39%; n 5 14), contusion (28%; n 5 10), fatigue (25%; n 5 9), and cough (22%; n 5 8) in FL patients. Neutropenia was the most common grade 3/4 AE (CLL/SLL, 31% [n 5 14]; FL, 14% [n 5 5]). Five patients required temporary dose reductions, and 5 discontinued the study drug because of AEs. Overall response rate (ORR) was 100% (n520) in treatment-naive CLL patients and 92% (n523) in R/R CLL patients. ORR in 36 R/R FL patients was 72% (n 5 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.

Original languageEnglish
Pages (from-to)4802-4811
Number of pages10
JournalBlood advances
Volume4
Issue number19
DOIs
Publication statusPublished - Oct 2020

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