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Title: Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukaemia and follicular lymphoma.
Epworth Authors: Prince, Miles
Other Authors: Tam, Constantine
Quach, Hang
Nicol, Andrew
Badoux, Xavier
Rose, Hannah
Leahy, Michael
Wickham, Nicholas
Patil, Sushrut
Huang, Jane
Prathikanti, Radha
Cohen, Aileen
Elstrom, Rebecca
Reed, William
Schneider, Jingjing
Flinn, Ian
Keywords: Zanubrutinib (BGB-3111)
Chronic Lymphocytic Leukemia (CLL)
Bruton Tyrosine Kinase Inhibitor
Phase 1b Study
Early Efficacy
Small Lymphocytic Lymphoma (SLL)
Relapsed/Refractory (R/R)
Follicular Lymphoma (FL)
Recommended Phase 2 Doses (RP2Ds)
Preliminary Antitumor Activity
B-cell Malignancies
Dose-Limiting Toxicity (DLT)
Kaplan-Meier Method
Anti-CD20 Antibodies
Progression-Free Survival (PFS)
Overall Survival
Ibrutinib Monotherapy
Off-Target Effects
Common Adverse Events (AEs)
DLT assessment
Duration of Response (DOR)
Marginal Zone lLmphoma
Infusion-Related Reactions
Interleukin-2–Inducible T-cell Kinase (ITK
Epidermal Growth Factor Receptor (EGFR
X-Linked Agammaglobulinemia
Treatment-Naïve (TN)
Preliminary Antitumor Activity
Obinutuzumab Infusions
Peripheral Blood Minimal Residual Disease (MRD)
Complete Response (CR)
Progressive Disease (PD)
Epworth Centre for Immunotherapies and Snowdome Laboratories
Molecular Oncology and Cancer Immunology
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
Issue Date: Oct-2020
Publisher: American Society of Hematology
Citation: Blood Adv (2020) 4 (19): 4802–4811.
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 as #NCT02569476. In conclusion, our results demonstrate that the combination of zanubrutinib and obinutuzumab seems tolerable in CLL and FL and clinical responses were observed. The study is limited by its preliminary nature, small number of patients, and lack of a control group. The safety results of this trial, particularly the relatively low rate of AEs requiring treatment discontinuation, support continued evaluation of this combination. A global randomized phase 2 study of the combination is currently enrolling patients with R/R FL. For CLL/SLL, alternative novel combinations are being evaluated.
DOI: 10.1182/bloodadvances.2020002183
PubMed URL:
ISSN: 2473-9537
Journal Title: Blood Advances
Type: Journal Article
Affiliated Organisations: Peter MacCallum Cancer Centre, St Vincent's Hospital, Royal Melbourne Hospital, University of Melbourne, Melbourne, VIC, Australia
Department of Haematology, St Vincent's Hospital, University of Melbourne, Melbourne VIC, Australia
Brisbane Clinic for Lymphoma, Myeloma, and Leukaemia, Brisbane, QLD, Australia
Department of Haematology, St George Hospital, Sydney, NSW, Australia
University Hospital, Geelong, VIC, Australia
Department of Haematology, Royal Perth Hospital, University of Western Australia, Perth, WA, Australia
Border Medical Oncology, Albury, NSW, Australia
Ashford Cancer Centre Research, Adelaide Cancer Centre, Adelaide, SA, Australia
Alfred Hospital and Monash University, Melbourne, VIC, Australia
BeiGene USA, Inc., San Mateo, CA
Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN
Type of Clinical Study or Trial: Clinical Trial
Appears in Collections:Cancer Services

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