Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial.

Autor:	Hutchings M; Department of Hematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark., Morschhauser F; Université de Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France., Iacoboni G; Department of Hematology, Vall d'Hebron University Hospital, Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.; Department of Medicine, Universitat Autònoma of Barcelona, Barcelona, Spain., Carlo-Stella C; Humanitas Clinical and Research Center-IRCCS and Humanitas University, Rozzano, Italy., Offner FC; Ghent University, Ghent, Belgium., Sureda A; Institut Català d'Oncologia-Hospitalet, Institut d'Investigació Biomedica de Bellvitge, Universitat de Barcelona, Barcelona, Spain., Salles G; Hôpital Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite, France., Martínez-Lopez J; Hospital 12 de Octubre, i+12, Complutense University, Centro Nacional de Investigaciones Oncológicas, CRIS Unit, Madrid, Spain., Crump M; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada., Thomas DN; Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY., Morcos PN; Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY., Ferlini C; Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY., Bröske AE; Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany., Belousov A; Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland., Bacac M; Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland., Dimier N; Roche Innovation Center Welwyn, Roche Pharma Research and Early Development, Welwyn Garden City, United Kingdom., Carlile DJ; Roche Innovation Center Welwyn, Roche Pharma Research and Early Development, Welwyn Garden City, United Kingdom., Lundberg L; Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland., Perez-Callejo D; Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland., Umaña P; Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland., Moore T; Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany., Weisser M; Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany., Dickinson MJ; Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2021 Jun 20; Vol. 39 (18), pp. 1959-1970. Date of Electronic Publication: 2021 Mar 19.
DOI:	10.1200/JCO.20.03175
Abstrakt:	Purpose: Glofitamab is a T-cell-engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt ) to reduce toxicity, are presented. Methods: Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt . Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab. Results: Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell-associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation. Conclusion: In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile. Competing Interests: Martin HutchingsConsulting or Advisory Role: Takeda, Roche, GenmabResearch Funding: Celgene, Genmab, Roche, Takeda, Novartis Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Gloria IacoboniHonoraria: Gilead Sciences, Novartis, Roche/Genentech, Celgene/Bristol Myers Squibb, JanssenConsulting or Advisory Role: Novartis, Celgene/Bristol Myers Squibb, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Novartis, Celgene/Bristol Myers Squibb Carmelo Carlo-StellaHonoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca, Celgene, Takeda, Incyte, Gilead SciencesConsulting or Advisory Role: Sanofi, ADC Therapeutics, Roche, Karyopharm Therapeutics, Celgene/Bristol Myers Squibb, IncyteResearch Funding: ADC Therapeutics, Sanofi, RocheTravel, Accommodations, Expenses: Roche, Janssen, Takeda, ADC Therapeutics Anna SuredaHonoraria: Takeda, Bristol Myers Squibb, Merck Sharp & Dohme, Celgene, Janssen, Sanofi, Roche, Novartis, Gilead Sciences, Janssen-CilagConsulting or Advisory Role: Takeda, Bristol Myers Squibb, Gilead Sciences, Celgene, Janssen, NovartisSpeakers' Bureau: TakedaOther Relationship: Sanofi, Takeda, Roche, Celgene, Gilead Sciences Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, Bristol Myers Squibb, BeiGene, Incyte, Miltenyi Biotec Joaquín Martínez-LopezSpeakers' Bureau: Roche, Janssen-Cilag, BMSiResearch Funding: Astellas Pharma, Bristol Myers Squibb Michael CrumpHonoraria: Gilead Sciences, Servier/PfizerConsulting or Advisory Role: Servier, Gilead Sciences, Novartis Canada Pharmaceuticals IncResearch Funding: Roche Canada Denise N. ThomasEmployment: Roche TCRC, Genmab, Cellectis Peter N. MorcosEmployment: Roche/Genentech, BayerStock and Other Ownership Interests: Roche/Genentech, Bayer Cristiano FerliniEmployment: Roche/Genentech, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Ann-Marie E. BröskeEmployment: RocheStock and Other Ownership Interests: Roche, BioNTech AG Anton BelousovEmployment: Roche Marina BacacEmployment: RocheStock and Other Ownership Interests: RocheResearch Funding: RochePatents, Royalties, Other Intellectual Property: Coinventor in Roche patentsTravel, Accommodations, Expenses: Roche Natalie DimierEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche David J. CarlileEmployment: Roche, AstraZenecaStock and Other Ownership Interests: AstraZeneca, Roche Linda LundbergEmployment: F. Hoffmann LaRocheStock and Other Ownership Interests: F. Hoffmann LaRoche David Perez-CallejoEmployment: RocheStock and Other Ownership Interests: Roche Pablo UmañaEmployment: RocheLeadership: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: Co-inventor in Roche-owned patents on glofitamab and obinutuzumabTravel, Accommodations, Expenses: Roche Tom MooreEmployment: RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche Martin WeisserEmployment: RocheStock and Other Ownership Interests: RochePatents, Royalties, Other Intellectual Property: I hold patents for biomarkers and drug combinations. These are not related to the present study. I do not receive royalties Michael J. DickinsonHonoraria: Roche, Amgen, MSD, Janssen, Bristol Myers Squibb, NovartisConsulting or Advisory Role: Novartis, Bristol Myers Squibb, Gilead Sciences, Roche, JanssenSpeakers' Bureau: NovartisResearch Funding: Novartis, Roche, Takeda, Celgene, MSDTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.
Databáze:	MEDLINE
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