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
| Autor: | Martin Weisser, Michael Dickinson, Gilles Salles, Michael Crump, Ann-Marie E Bröske, Peter N. Morcos, Carmelo Carlo-Stella, David Perez-Callejo, Natalie Dimier, Marina Bacac, Tom Moore, Franck Morschhauser, David Carlile, Denise Thomas, Cristiano Ferlini, Fritz Offner, Pablo Umana, Linda Lundberg, Martin Hutchings, Anton Belousov, Joaquin Martinez-Lopez, Gloria Iacoboni, Anna Sureda |
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| Přispěvatelé: | Institut Català de la Salut, [Hutchings M] Department of Hematology and Phase 1 Unit, Rigshospitalet, Copenhagen, Denmark. [Morschhauser F] Université de Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France. [Iacoboni G] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Carlo-Stella C] Humanitas Clinical and Research Center—IRCCS and Humanitas University, Rozzano, Italy. [Offner FC] Ghent University, Ghent, Belgium. [Sureda A] Institut Català d’Oncologia-Hospitalet, Institut d’Investigació Biomèdica de Bellvitge, Universitat de Barcelona, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Lymphoma B-Cell Neoplasms::Neoplasms by Histologic Type::Lymphoma::Lymphoma Non-Hodgkin::Lymphoma B-Cell [DISEASES] T-Lymphocytes T cell CD3 Cèl·lules B - Tumors - Tractament aminoácidos péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos biespecíficos [COMPUESTOS QUÍMICOS Y DROGAS] neoplasias::neoplasias por tipo histológico::linfoma::linfoma no Hodgkin::linfoma de células B [ENFERMEDADES] Bivalent (genetics) Young Adult Antineoplastic Agents Immunological Internal medicine Antibodies Bispecific Lymphatic diseases medicine Medicine and Health Sciences Humans Otros calificadores::/terapia [Otros calificadores] Aged Aged 80 and over CD20 Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores] Hematology biology Malalties del sistema limfàtic business.industry Cancer Other subheadings::/therapy [Other subheadings] Middle Aged Antigens CD20 medicine.disease Immunoglobulines - Ús terapèutic Lymphoma medicine.anatomical_structure Oncology Sang - Malalties biology.protein Cancer research Other subheadings::Other subheadings::/administration & dosage [Other subheadings] Female Monoclonal antibodies Antibody Amino Acids Peptides and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies Bispecific [CHEMICALS AND DRUGS] business Anticossos monoclonals |
| Zdroj: | JOURNAL OF CLINICAL ONCOLOGY Scientia Dipòsit Digital de la UB Universidad de Barcelona |
| ISSN: | 0732-183X 1527-7755 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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