Abstract
Background: Relapsed/refractory pediatric central nervous system (CNS) tumors have a poor prognosis. Epidermal growth factor receptor (EGFR) is commonly overexpressed, but EGFRvIII mutations are uncommon. To target these tumors, we used chimeric antigen receptor (CAR) T cells with a binder based on mAb806 which recognizes ectopically expressed wild-type EGFR and EGFRvIII. Methods: In this open-label phase 1 clinical trial, patients aged 1-26 years with EGFR + CNS tumors received weekly infusions of 1-2.5 × 107 CAR T cells into the tumor resection bed or the lateral ventricle via an implanted catheter. No lymphodepletion was used. Results: Eleven patients were enrolled. Four (3 with high-grade glioma, 1 with atypical teratoid rhabdoid tumor) were treated and received 5-10 CAR T cell infusions without dose-limiting toxicities. The trial closed prior to reaching planned dose regimens. All treatment-related adverse events were no higher than CTCAE grade 2. The most common were headache and nausea. One patient had a grade 1 seizure, and 3 had new sensory changes, weakness and/or urinary changes (grades 1-2) that were possibly related to CAR T cell infusion. A total of 3 of the 4 treated patients had progressive disease. One patient with spinal cord diffuse midline glioma had progressive peritumoral edema that could not be conclusively attributed to either progression or pseudoprogression and was, therefore, defined as stable disease, followed by a complete response to subsequent chemotherapy. Conclusions: Intracranially infused EGFR806-CAR T cells were tolerable at tested doses, with the best response of stable disease. EGFR is a potentially useful target for cellular therapy against pediatric brain tumors, particularly high-grade gliomas.