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. - Université de Lille Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2021

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.

M. Hutchings
  • Fonction : Auteur
G. Iacoboni
  • Fonction : Auteur
C. Carlo-Stella
  • Fonction : Auteur
F. C. Offner
  • Fonction : Auteur
A. Sureda
  • Fonction : Auteur
G. Salles
  • Fonction : Auteur
J. Martínez-Lopez
  • Fonction : Auteur
M. Crump
  • Fonction : Auteur
D. N. Thomas
  • Fonction : Auteur
P. N. Morcos
  • Fonction : Auteur
C. Ferlini
  • Fonction : Auteur
A. E. Bröske
  • Fonction : Auteur
A. Belousov
  • Fonction : Auteur
M. Bacac
  • Fonction : Auteur
N. Dimier
  • Fonction : Auteur
D. J. Carlile
  • Fonction : Auteur
L. Lundberg
  • Fonction : Auteur
D. Perez-Callejo
  • Fonction : Auteur
P. Umaña
  • Fonction : Auteur
T. Moore
  • Fonction : Auteur
M. Weisser
  • Fonction : Auteur
M. J. Dickinson
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04197279 , version 1 (06-09-2023)

Identifiants

Citer

M. Hutchings, Franck Morschhauser, G. Iacoboni, C. Carlo-Stella, F. C. Offner, et al.. 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.. Journal of Clinical Oncology, 2021, Journal of Clinical Oncology, 39 (18), pp.1959-1970. ⟨10.1200/JCO.20.03175⟩. ⟨hal-04197279⟩

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