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DC Field | Value | Language |
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dc.contributor.author | Trotman J. | en |
dc.contributor.author | Marlton P. | en |
dc.contributor.author | Munoz J. | en |
dc.contributor.author | Seymour J.F. | en |
dc.contributor.author | Simpson D. | en |
dc.contributor.author | Tedeschi A. | en |
dc.contributor.author | Elstrom R. | en |
dc.contributor.author | Yu Y. | en |
dc.contributor.author | Tang Z. | en |
dc.contributor.author | Han L. | en |
dc.contributor.author | Huang J. | en |
dc.contributor.author | Novotny W. | en |
dc.contributor.author | Wang L. | en |
dc.contributor.author | Harrup R. | en |
dc.contributor.author | Roberts A.W. | en |
dc.contributor.author | Gottlieb D. | en |
dc.contributor.author | Burger J.A. | en |
dc.contributor.author | Opat S. | en |
dc.contributor.author | Tam C.S. | en |
dc.contributor.author | Johnston P.B. | en |
dc.contributor.author | Cull G. | en |
dc.date.accessioned | 2021-05-14T12:11:17Z | en |
dc.date.available | 2021-05-14T12:11:17Z | en |
dc.date.copyright | 2019 | en |
dc.date.created | 20190926 | en |
dc.date.issued | 2019-09-26 | en |
dc.identifier.citation | Blood. 134 (11) (pp 851-859), 2019. Date of Publication: 12 Sep 2019. | en |
dc.identifier.issn | 0006-4971 | en |
dc.identifier.uri | https://repository.monashhealth.org/monashhealthjspui/handle/1/35986 | en |
dc.description.abstract | Zanubrutinib is a potent and highly selective inhibitor of Bruton tyrosine kinase (BTK). In this first-in-human, open-label, multicenter, phase 1 study, patients in part 1 (3 1 3 dose escalation) had relapsed/refractory B-cell malignancies and received zanubrutinib 40, 80, 160, or 320 mg once daily or 160 mg twice daily. Part 2 (expansion) consisted of disease-specific cohorts, including treatment-naive or relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL). The primary end points were safety and tolerability, and definition of the maximum tolerated dose (part 1). Additional end points included pharmacokinetics/pharmacodynamics and preliminary efficacy. Reported herein are results from 144 patients enrolled in the dose-finding and CLL/SLL cohorts. No dose-limiting toxicities occurred in dose escalation. Median BTK occupancy in peripheral blood mononuclear cells was >95% at all doses. Sustained complete (>95%) BTK occupancy in lymph node biopsy specimens was more frequent with 160 mg twice daily than 320 mg once daily (89% vs 50%; P 5 .0342). Consequently, 160 mg twice daily was selected for further investigation. With median follow-up of 13.7 months (range, 0.4-30.5 months), 89 CLL/SLL patients (94.7%) remain on study. Most toxicities were grade 1/2; neutropenia was the only grade 3/4 toxicity observed in >2 patients. One patient experienced a grade 3 subcutaneous hemorrhage. Among 78 efficacy-evaluable CLL/SLL patients, the overall response rate was 96.2% (95% confidence interval, 89.2-99.2). Estimated progression-free survival at 12 months was 100%. Zanubrutinib demonstrated encouraging activity in CLL/SLL patients, with a low incidence of major toxicities.Copyright © 2019 by The American Society of Hematology | en |
dc.language | English | en |
dc.language | en | en |
dc.publisher | American Society of Hematology (E-mail: publishing@hematology.org) | en |
dc.relation.ispartof | Blood | en |
dc.title | Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. | en |
dc.type | Article | en |
dc.type.studyortrial | Observational study (cohort, case-control, cross sectional or survey) | - |
dc.identifier.doi | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1182/blood.2019001160 | en |
dc.publisher.place | United States | en |
dc.identifier.pubmedid | 31340982 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31340982] | en |
dc.identifier.source | 2002929383 | en |
dc.identifier.institution | (Tam, Seymour, Roberts) Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (Tam, Seymour, Roberts) Department of Medicine, University of Melbourne, Parkville, VIC, Australia (Tam) St Vincent's Hospital, Fitzroy, VIC, Australia (Tam, Seymour, Roberts) Royal Melbourne Hospital, Parkville, VIC, Australia (Tam, Seymour, Roberts) Victorian Comprehensive Cancer Centre, Melbourne, VIC, Australia (Trotman) Department of Haematology, Concord Repatriation General Hospital, Concord, NSW, Australia (Trotman) Haematology Department, University of Sydney, Concord, NSW, Australia (Opat) Clinical Haematology, Monash Health, Clayton, VIC, Australia (Opat) School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia (Burger) Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, United States (Cull) Haematology Department, Sir Charles Gairdner Hospital, Nedlands, WA, Australia (Cull) PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia (Cull) University of Western Australia, Perth, WA, Australia (Gottlieb) Department of Medicine, Sydney Medical School, University of Sydney, Sydney, NSW, Australia (Gottlieb) Department of Haematology, Westmead Hospital, Westmead, NSW, Australia (Harrup) Department of Clinical Haematology, Royal Hobart Hospital, Hobart, TAS, Australia (Harrup) Department of Medical Oncology, University of Tasmania, Hobart, TAS, Australia (Johnston) Division of Hematology, Mayo Clinic, Rochester, MN, United States (Marlton) Princess Alexandra Hospital, Brisbane, QLD, Australia (Marlton) School of Medicine, University of Queensland, Brisbane, QLD, Australia (Munoz) Banner MD Anderson Cancer Center, Gilbert, AZ, United States (Simpson) North Shore Hospital, Auckland, New Zealand (Tedeschi) ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy (Elstrom, Tang, Han, Huang, Novotny) BeiGene USA, Inc, San Mateo, CA, United States (Yu) BeiGene Shanghai, Ltd, Shanghai, China (Wang) BeiGene Beijing, Ltd, Beijing, China (Roberts) Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia | en |
dc.description.address | C.S. Tam, Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, VIC 3050, Australia. E-mail: constantine.tam@petermac.org | en |
dc.description.publicationstatus | Embase | en |
dc.rights.statement | Copyright 2019 Elsevier B.V., All rights reserved. | en |
dc.identifier.authoremail | Tam C.S.; constantine.tam@petermac.org | en |
item.cerifentitytype | Publications | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
item.openairetype | Article | - |
crisitem.author.dept | Haematology | - |
Appears in Collections: | Articles |
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