PMID- 33022066
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210925
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 4
IP  - 19
DP  - 2020 Oct 13
TI  - Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic 
      leukemia and follicular lymphoma.
PG  - 4802-4811
LID - 10.1182/bloodadvances.2020002183 [doi]
AB  - 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.
CI  - (c) 2020 by The American Society of Hematology.
FAU - Tam, Constantine S
AU  - Tam CS
AD  - Peter MacCallum Cancer Centre, St Vincent's Hospital, Royal Melbourne Hospital, 
      University of Melbourne, Melbourne, VIC, Australia.
FAU - Quach, Hang
AU  - Quach H
AD  - Department of Haematology, St Vincent's Hospital, University of Melbourne, 
      Melbourne, VIC, Australia.
FAU - Nicol, Andrew
AU  - Nicol A
AD  - Brisbane Clinic for Lymphoma, Myeloma, and Leukaemia, Brisbane, QLD, Australia.
FAU - Badoux, Xavier
AU  - Badoux X
AD  - Department of Haematology, St George Hospital, Sydney, NSW, Australia.
FAU - Rose, Hannah
AU  - Rose H
AD  - University Hospital, Geelong, VIC, Australia.
FAU - Prince, H Miles
AU  - Prince HM
AD  - Epworth Healthcare, Peter MacCallum Department of Oncology, University of 
      Melbourne, Melbourne, VIC, Australia.
FAU - Leahy, Michael F
AU  - Leahy MF
AD  - Department of Haematology, Royal Perth Hospital, University of Western Australia, 
      Perth, WA, Australia.
FAU - Eek, Richard
AU  - Eek R
AD  - Border Medical Oncology, Albury, NSW, Australia.
FAU - Wickham, Nicholas
AU  - Wickham N
AD  - Ashford Cancer Centre Research, Adelaide Cancer Centre, Adelaide, SA, Australia.
FAU - Patil, Sushrut S
AU  - Patil SS
AD  - Alfred Hospital and Monash University, Melbourne, VIC, Australia.
FAU - Huang, Jane
AU  - Huang J
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Prathikanti, Radha
AU  - Prathikanti R
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Cohen, Aileen
AU  - Cohen A
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Elstrom, Rebecca
AU  - Elstrom R
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Reed, William
AU  - Reed W
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Schneider, Jingjing
AU  - Schneider J
AD  - BeiGene USA, Inc., San Mateo, CA; and.
FAU - Flinn, Ian W
AU  - Flinn IW
AD  - Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN.
LA  - eng
SI  - ClinicalTrials.gov/NCT02569476
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyrimidines)
RN  - AG9MHG098Z (zanubrutinib)
RN  - O43472U9X8 (obinutuzumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized
MH  - Humans
MH  - *Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
MH  - *Lymphoma, Follicular
MH  - Piperidines
MH  - Pyrazoles
MH  - Pyrimidines/adverse effects
PMC - PMC7556127
COIS- Conflict-of-interest disclosure: C.S.T. received research funding from Janssen, 
      AbbVie, BeiGene, Pharmacyclics, and TG Therapeutics and served as a consultant 
      for BeiGene, Janssen, Roche, AbbVie, and LOXO. H.Q. served as a consultant for 
      Celgene, Janssen Cilag, Takeda, Karyopharm, and Amgen and received research 
      funding from Celgene and Amgen. A.N. received research funding from Parexel and 
      travel funding from Amgen, Janssen, and Novartis. X.B. received honoraria from 
      Roche and served as a consultant for AbbVie. H.M.P. received honoraria from 
      Takeda, Janssen, Amgen, Celgene, and Allergan; served as a consultant for Takeda, 
      Janssen, Amgen, and Allergan; and received research funding from Allergan. M.F.L. 
      received honoraria from Vifor Pharma and travel funding from Amgen. N.W. has 
      equity ownership in Icon Consolidated Holdings and received travel funding from 
      Celgene. J.H. is an employee of, has a leadership role in, and has equity 
      ownership in BeiGene USA. A.C. is an employee of, has equity ownership in, and 
      received travel funding from BeiGene USA. R.E. is an employee of BeiGene and has 
      equity ownership in BeiGene USA and Roche. R.P. is an employee of BeiGene USA and 
      has equity ownership in BeiGene USA and Amgen. W.R. is an employee of, has equity 
      ownership in, and received travel funding from BeiGene USA. J.S. is an employee 
      of and has equity ownership in BeiGene USA. I.W.F. served as a consultant for 
      AbbVie, Seattle Genetics, TG Therapeutics, and Verastem and received research 
      funding from Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation 
      Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, 
      Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola 
      Pharmaceuticals, Roche, TG Therapeutics, Trilliam Therapeutics, AbbVie, ArQule, 
      BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, 
      Verastem, Gilead Sciences, AstraZeneca, Juno Therapeutics, Unum Therapeutics, and 
      MorphoSys. The remaining authors declare no competing financial interests.
EDAT- 2020/10/07 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/10/06
CRDT- 2020/10/06 17:12
PHST- 2020/04/29 00:00 [received]
PHST- 2020/08/07 00:00 [accepted]
PHST- 2020/10/06 17:12 [entrez]
PHST- 2020/10/07 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/10/06 00:00 [pmc-release]
AID - S2473-9529(20)31211-8 [pii]
AID - 2020/ADV2020002183 [pii]
AID - 10.1182/bloodadvances.2020002183 [doi]
PST - ppublish
SO  - Blood Adv. 2020 Oct 13;4(19):4802-4811. doi: 10.1182/bloodadvances.2020002183.