Phase I Trial Evaluating Locoregionally-delivered IL13Rα2-targeting CAR T Cells in High-Grade Glioma
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ABSTRACT: We report here a phase I trial (NCT02208362) evaluating locoregional delivery of IL13Rα2-targeted CAR T cells in 65 patients with recurrent high-grade glioma, the majority being recurrent glioblastoma (rGBM). Primary objectives were to evaluate safety and feasibility, and secondary objectives were to assess therapy-related cytokine dynamics, CAR T cell persistence and clinical outcomes. Feasibility and safety were established for three routes of locoregional CAR T cell administration [intratumoral (ICT), intraventricular (ICV) and dual ICT/ICV], with IL13Rα2-CAR T cells being well-tolerated with clinically manageable adverse events at all dose levels. Stable disease or better was achieved in 50% of patients, with two partial responses, one complete response (CR), and a second CR after additional CAR T cycles off protocol therapy. Patients with rGBM treated on Arm 5, utilizing dual ICT/ICV delivery and an optimized manufacturing process exhibited the best overall survival of 10.2 months. . Central nervous system (CNS) increases in inflammatory cytokines, including IFNγ, CXCL9, and CXCL10, were associated with CAR T cell administration and bioactivity. Further, pre-treatment intratumoral CD3 T cell levels were positively associated with survival, suggesting an interplay between host immunity and CAR T cells as a determinant of outcomes. These findings advance our understanding of CAR T cell immunotherapy for malignant brain tumors. ClinicalTrials.gov Identifier: NCT02208362
ORGANISM(S): Homo sapiens
PROVIDER: GSE255850 | GEO | 2024/02/20
REPOSITORIES: GEO
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