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

  • J Clin Oncol. 2021 Jun 20;39(18):1959-1970. doi: 10.1200/JCO.20.03175.
Martin Hutchings  1 ,  Franck Morschhauser  2 ,  Gloria Iacoboni  3  4 ,  Carmelo Carlo-Stella  5 ,  Fritz C Offner  6 ,  Anna Sureda  7 ,  Gilles Salles  8 ,  Joaquín Martínez-Lopez  9 ,  Michael Crump  10 ,  Denise N Thomas  11 ,  Peter N Morcos  11 ,  Cristiano Ferlini  11 ,  Ann-Marie E Bröske  12 ,  Anton Belousov  13 ,  Marina Bacac  13 ,  Natalie Dimier  14 ,  David J Carlile  14 ,  Linda Lundberg  15 ,  David Perez-Callejo  15 ,  Pablo Umaña  13 ,  Tom Moore  12 ,  Martin Weisser  12 ,  Michael J Dickinson  16
Affiliations
  • 1. Department of Hematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark.
  • 2. Université de Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, 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.
  • 4. Department of Medicine, Universitat Autònoma of Barcelona, Barcelona, Spain.
  • 5. Humanitas Clinical and Research Center-IRCCS and Humanitas University, Rozzano, Italy.
  • 6. Ghent University, Ghent, Belgium.
  • 7. Institut Català d'Oncologia-Hospitalet, Institut d'Investigació Biomedica de Bellvitge, Universitat de Barcelona, Barcelona, Spain.
  • 8. Hôpital Lyon Sud, Université Claude Bernard Lyon 1, Pierre-Bénite, France.
  • 9. Hospital 12 de Octubre, i+12, Complutense University, Centro Nacional de Investigaciones Oncológicas, CRIS Unit, Madrid, Spain.
  • 10. Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
  • 11. Roche Innovation Center New York, Roche Pharma Research and Early Development, New York, NY.
  • 12. Roche Innovation Center Munich, Roche Pharma Research and Early Development, Penzberg, Germany.
  • 13. Roche Innovation Center Zurich, Roche Pharma Research and Early Development, Zurich, Switzerland.
  • 14. Roche Innovation Center Welwyn, Roche Pharma Research and Early Development, Welwyn Garden City, United Kingdom.
  • 15. Roche Innovation Center Basel, Roche Pharma Research and Early Development, Basel, Switzerland.
  • 16. Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
PMID: 33739857 DOI: 10.1200/JCO.20.03175
Abstract

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.

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