Glofitamab, a Novel, Bivalent CD20-Targeting ...
Type de document :
Article dans une revue scientifique: Article original
DOI :
PMID :
URL permanente :
Titre :
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.
Auteur(s) :
Hutchings, M. [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Iacoboni, G. [Auteur]
Carlo-Stella, C. [Auteur]
Offner, F. C. [Auteur]
Sureda, A. [Auteur]
Salles, G. [Auteur]
Martínez-Lopez, J. [Auteur]
Crump, M. [Auteur]
Thomas, D. N. [Auteur]
Morcos, P. N. [Auteur]
Ferlini, C. [Auteur]
Bröske, A. E. [Auteur]
Belousov, A. [Auteur]
Bacac, M. [Auteur]
Dimier, N. [Auteur]
Carlile, D. J. [Auteur]
Lundberg, L. [Auteur]
Perez-Callejo, D. [Auteur]
Umaña, P. [Auteur]
Moore, T. [Auteur]
Weisser, M. [Auteur]
Dickinson, M. J. [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365
Iacoboni, G. [Auteur]
Carlo-Stella, C. [Auteur]
Offner, F. C. [Auteur]
Sureda, A. [Auteur]
Salles, G. [Auteur]
Martínez-Lopez, J. [Auteur]
Crump, M. [Auteur]
Thomas, D. N. [Auteur]
Morcos, P. N. [Auteur]
Ferlini, C. [Auteur]
Bröske, A. E. [Auteur]
Belousov, A. [Auteur]
Bacac, M. [Auteur]
Dimier, N. [Auteur]
Carlile, D. J. [Auteur]
Lundberg, L. [Auteur]
Perez-Callejo, D. [Auteur]
Umaña, P. [Auteur]
Moore, T. [Auteur]
Weisser, M. [Auteur]
Dickinson, M. J. [Auteur]
Titre de la revue :
Journal of Clinical Oncology
Nom court de la revue :
J Clin Oncol
Numéro :
39
Pagination :
1959-1970
Éditeur :
American Society of Clinical Oncology
Date de publication :
2021-03-20
ISSN :
1527-7755
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Langue :
Anglais
Audience :
Internationale
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Date de dépôt :
2023-05-25T03:12:40Z
2023-09-06T06:23:03Z
2023-09-06T06:23:03Z