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Conference/Presentation Title: | Preliminary safety and efficacy data from patients (PTS) with relapsed/refractory (r/r) b-cell malignancies treated with the novel b-cell lymphoma 2 (bcl2) inhibitor bgb-11417 in monotherapy or in combination with zanubrutinib. | Authors: | Ghia P.;Tam C.;Verner E.;Lasica M.;Arbelaez A.;Browett P.;Soumerai J.;Hilger J.;Fang Y.;Huang J.;Simpson D.;Opat S. ;Cheah C. | Institution: | (Ghia) Universita Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Italy (Tam) Peter MacCallum Cancer Centre, Australia (Tam) University of Melbourne, Australia (Tam, Lasica) St Vincent's Hospital Melbourne, Australia (Tam) Royal Melbourne Hospital, Australia (Verner) Concord Repatriation General Hospital, Australia (Verner) University of Sydney, Australia (Arbelaez) John Flynn Private Hospital, Australia (Arbelaez) Pindara Private Hospital, Australia (Browett) Department of Haematology, Auckland City Hospital, New Zealand (Soumerai) Massachusetts General Hospital Cancer Center, Harvard Medical School, United States (Hilger, Fang, Huang, Simpson) BeiGene (Shanghai) Co., Ltd. and BeiGene USA, Inc., United States (Opat) Monash Health, Australia (Opat) Monash University, Australia (Cheah) Department of Haematology, Sir Charles Gairdner Hospital and Pathwest Laboratory Medicine, Australia (Cheah) Medical School, University of Western Australia, Australia (Cheah) Linear Clinical Research, Australia |
Presentation/Conference Date: | 27-May-2022 | Copyright year: | 2022 | Publisher: | Ferrata Storti Foundation | Publication information: | Haematologica. Conference: 17th Congress of the Italian Society of Experimental Hematology. Roma Italy. 107(SUPPL 1) (pp 33-34), 2022. Date of Publication: March 2022. | Journal: | Haematologica | Abstract: | Introduction: BGB-11417, a potent and highly selective BCL2 inhibitor, had superior antitumor activity vs venetoclax (approved BCL2 inhibitor) in human acute lymphoblastic leukemia, mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma xenograft models. BGB-11417 had a favorable PK profile with excellent bioavailability and BCL2 selectivity at <1 nM. Toxicology studies showed a broad therapeutic index and tolerable safety profile. Zanubrutinib (zanu), a next-generation BTK inhibitor with excellent activity and favorable toxicity in pts with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and MCL, is approved for MCL, R/R marginal zone lymphoma, and Waldenstrom's macroglobulinemia (WM). Combining BCL2+BTK inhibitors is tolerable with synergistic activity in CLL and MCL. Method(s): BGB-11417-101 (NCT04277637), a phase 1, open-label, multicenter, dose-escalation/expansion study, examined BGB-11417 +/- zanu in non-Hodgkin lymphoma (NHL) or CLL/SLL. For dose escalation, pts with R/R B-cell malignancies were enrolled in 1 of 5 BGB- 11417 dose cohorts (40, 80, 160, 320, or 640 mg QD). All pts used a ramp-up to intended target dose that varied by disease. Pts in the combination arm received zanu 320 mg daily starting 8-12 wks before BGB- 11417 introduction. Adverse events (AEs) were reported per Common Terminology Criteria for AEs v5.0. Dose-limiting toxicity (DLT) was assessed from ramp-up through day 21 at intended daily dose; Bayesian logistic regression determined the maximum tolerated dose. Result(s): As of 24 May 2021 (data cutoff) 19 pts were treated; 14 with monotherapy (NHL: n=11; CLL/SLL: n=3) and 5 with combination (all CLL; 3 on zanu pretreatment; 2 started combination). All pts (median age, 72 y) were R/R (median of 2 prior regimens); median follow-up was 1.9 mo. No DLTs were seen in pts with NHL receiving BGB-11417 alone (n=11) up to 160 mg. Reported AEs across all doses are shown in Table 1. Five pts (all NHL) discontinued treatment (disease progression, n=4 [2 at 40 mg, 2 at 80 mg]; lack of efficacy, n=1 [40 mg]). No pt discontinued due to AEs. Laboratory tumor lysis syndrome was observed in 1 pt with CLL and high tumor burden (resolved with no sequelae). Initial efficacy after 3-mo restaging in pts with CLL/SLL had 1 one partial response (monotherapy) at the first dose level tested. All pts with CLL/SLL completing ramp-up (n=2, both monotherapy) normalized absolute lymphocyte count (ALC). Marked decreases in ALC occurred at doses as low as 1 mg (Figure 1). Conclusion(s): Preliminary results suggest BGB-11417 is tolerable in R/R NHL at the tested dose levels. Updated safety and efficacy data of BGB-11417+/-zanu in CLL/SLL and NHL will be presented; evaluation of treatment-naive CLL/SLL, R/R MCL, and R/R WM is planned. (Figure Presented). | Conference Name: | 17th Congress of the Italian Society of Experimental Hematology | Conference Start Date: | 2022-03-31 | Conference End Date: | 2022-04-02 | Conference Location: | Roma, Italy | DOI: | http://monash.idm.oclc.org/login?url= | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/47784 | Type: | Conference Abstract | Subjects: | absolute lymphocyte count adverse drug reaction cancer combination chemotherapy cancer patient cancer recurrence cancer resistance cancer size chronic lymphatic leukemia drug efficacy drug safety drug tolerability low drug dose lymphocytic lymphoma mantle cell lymphoma marginal zone lymphoma maximum tolerated dose monotherapy nomenclature nonhodgkin lymphoma plasmacytoma synergistic effect tumor lysis syndrome Waldenstroem macroglobulinemia Bruton tyrosine kinase inhibitor protein bcl 2 zanubrutinib |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Conferences |
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