Please use this identifier to cite or link to this item: https://repository.monashhealth.org/monashhealthjspui/handle/1/48928
Title: CLL-118 A Phase 1 Study With the Novel B-Cell Lymphoma 2 Inhibitor BGB-11417 as Monotherapy or in Combination With Zanubrutinib in Patients With B-Cell Malignancies: Preliminary Data.
Authors: Soumerai J.D.;Opat S. ;Cheah C.Y.;Lasica M.;Verner E.;Browett P.J.;Chan H.;Barca E.G.;Hilger J.;Fang Y.;Simpson D.;Tam C.S.
Institution: (Soumerai) Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States
(Opat) Monash Health, Clayton, Australia
(Opat) Monash University, Clayton, Australia
(Cheah) Sir Charles Gairdner Hospital and Pathwest Laboratory Medicine, Nedlands, Australia
(Cheah) Medical School, University of Western Australia, Crawley, Australia
(Cheah) Linear Clinical Research, Nedlands, Australia
(Lasica) St Vincent's Hospital Melbourne, Fitzroy, Australia
(Verner) Concord Repatriation General Hospital, Concord, Australia
(Verner) University of Sydney, Sydney, Australia
(Browett) Auckland City Hospital, Auckland, New Zealand
(Chan) North Shore Hospital Auckland, Auckland, New Zealand
(Barca) Institut Catala d'Oncologia-Hospitalet, IDIBELL, Universitat de-Barcelona, Barcelona, Spain
(Hilger, Fang, Simpson) BeiGene USA Inc., San Mateo, United States
(Tam) Peter MacCallum Cancer Centre, Melbourne, Australia
(Tam) University of Melbourne, Parkville, Australia
(Tam) Royal Melbourne Hospital, Parkville, Australia
Issue Date: 26-Sep-2022
Copyright year: 2022
Publisher: Elsevier Inc.
Place of publication: United States
Publication information: Clinical Lymphoma, Myeloma and Leukemia. 22(Supplement 2) (pp S267-S268), 2022. Date of Publication: October 2022.
Journal: Clinical Lymphoma, Myeloma and Leukemia
Abstract: Context: B-cell lymphoma 2 (BCL2) is aberrantly expressed in many hematologic malignancies and promotes tumorigenesis. BGB-11417-101 (NCT04277637) is an ongoing, first-in-human, phase 1/1b dose-escalation/expansion study evaluating the safety, tolerability, maximum tolerated dose (MTD), and recommended phase 2 dose of oral BGB-11417, a potent, highly selective BCL2 inhibitor, alone or in combination with zanubrutinib, a BTK inhibitor, in patients with relapsed/refractory (R/R) B-cell malignancies. Design(s): BGB-11417 (40, 80, 160, 320, or 640 mg once daily [QD]) with weekly or daily ramp-up to target dose was given as monotherapy or combined with zanubrutinib (320 mg QD or 160 mg twice daily) 8-12 weeks before BGB-11417. Dose-limiting toxicity was evaluated by Bayesian logistic regression. Adverse events (AEs) were reported per CTCAE v5.0. Result(s): As of December 17, 2021, 58 patients received BGB-11417 (monotherapy=32; combination=26). Of patients receiving monotherapy, 26 with non-Hodgkin lymphoma (NHL; 17 diffuse large B-cell lymphoma, 6 follicular lymphoma, and 3 marginal zone lymphoma) received <=640 mg and six with CLL/SLL received <=160 mg; for those receiving combination treatment, 19 with R/R CLL/SLL received BGB-11417 <=160 mg and seven with R/R MCL received <=80 mg. MTD has not been reached. Median follow-up was 3.9 months (range=0.1-20.4). Two grade >=3 AEs (neutropenia=1, autoimmune hemolytic anemia=1) occurred in combination cohorts. Twenty patients discontinued treatment (disease progression=17; AE=1; other=2). One high-risk patient with CLL (monotherapy) had laboratory tumor lysis syndrome (<2%) that resolved without intervention. Early data show that most patients had a reduction in the sum of products of perpendicular diameters; two patients with NHL (monotherapy) had responses (complete response=1). Patients with CLL/SLL had notable reductions in absolute lymphocyte counts at doses >=1 mg; two responses (>= partial response) occurred with monotherapy and 12 with combination treatment (>= partial response + lymphocytosis). Conclusion(s): Preliminary findings suggest that BGB-11417 has promising efficacy and is tolerable at <=640 mg as monotherapy and <=160 mg combined with zanubrutinib. Dose escalation continues as MTD has not been reached. Enrollment is ongoing; data for Waldenstrom macroglobulinemia and treatment-naive CLL/SLL are forthcoming.Copyright © 2022 Elsevier Inc.
DOI: http://monash.idm.oclc.org/login?url=https://dx.doi.org/10.1016/S2152-2650%2822%2901326-X
URI: https://repository.monashhealth.org/monashhealthjspui/handle/1/48928
Type: Article
Subjects: absolute lymphocyte count
autoimmune hemolytic anemia cancer combination chemotherapy
cancer patient
chronic lymphatic leukemia
diffuse large B cell lymphoma
follicular lymphoma
hematologic malignancy
high risk patient
lymphocytic lymphoma
lymphocytosis marginal zone lymphoma
maximum tolerated dose
monotherapy
neutropenia nonhodgkin lymphoma
tumor lysis syndrome antineoplastic agent
Type of Clinical Study or Trial: Clinical Trial
Appears in Collections:Articles

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