Hutchings et al. reported the safety, dosing, and clinical activity of single-dose glofitamab, a T cell engager with bivalency for CD20 on B cells and monovalency for CD3 on T cells, in relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Step-up dosing of 2.5mg, 10mg, and 30mg followed by 30mg at subsequent cycles was considered safe and was recommended as the Phase II dose (RP2D). Cytokine release syndrome was the most common adverse event, with low rates of grade 3 or higher cases. The ORR and CR for all doses were 53.8% and 36.8%, and for RP2D were 65.7% and 57.1%. At 27.4 months follow-up, 84.1% of CRs were maintained.
Contributed by Shishir Pant
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.
Author Info: (1) Department of Hematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark. (2) Universit de Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injecta
Author Info: (1) Department of Hematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark. (2) Universit de Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associes, Lille, France. (3) 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 Autnoma of Barcelona, Barcelona, Spain. (4) Humanitas Clinical and Research Center-IRCCS and Humanitas University, Rozzano, Italy. (5) Ghent University, Ghent, Belgium. (6) Institut Catal d'Oncologia-Hospitalet, Institut d'Investigaci Biomedica de Bellvitge, Universitat de Barcelona, Barcelona, Spain. (7) Hpital Lyon Sud, Universit Claude Bernard Lyon 1, Pierre-Bnite, France. (8) Hospital 12 de Octubre, i+12, Complutense University, Centro Nacional de Investigaciones Oncolgicas, CRIS Unit, Madrid, Spain. (9) Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada. (10) Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY. (11) Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY. (12) Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY. (13) Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany. (14) Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland. (15) Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland. (16) Roche Innovation Center Welwyn, Roche Pharma Research and Early Development, Welwyn Garden City, United Kingdom. (17) Roche Innovation Center Welwyn, Roche Pharma Research and Early Development, Welwyn Garden City, United Kingdom. (18) Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland. (19) Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland. (20) Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland. (21) Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany. (22) Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany. (23) Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
