Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide
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Published:2024-01
Issue:2
Volume:166
Page:321-330
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ISSN:0167-594X
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Container-title:Journal of Neuro-Oncology
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language:en
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Short-container-title:J Neurooncol
Author:
Fadul Camilo E.,Thakur Archana,Kim Jungeun,Kassay-McAllister Jessica,Schalk Dana,Lopes M. Beatriz,Donahue Joseph,Purow Benjamin,Dillon Patrick,Le Tri,Schiff David,Liu Qin,Lum Lawrence G.
Abstract
Abstract
Purpose
The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy.
Methods
This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ.
Results
The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009).
Conclusion
Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM.
ClinicalTrials.gov Identifier: NCT03344250
Funder
Brain Institute at the University of Virginia National Cancer Institute University of Virginia Cancer Center National Cancer Institute, USA
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Neurology (clinical),Neurology,Oncology
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