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.

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

Edité par CCSD ; American Society of Clinical Oncology -

International audience. PURPOSEGlofitamab 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.METHODSSeven 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.RESULTSFollowing 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.CONCLUSIONIn patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile.

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