45084 CARv3-TEAM-E T cells for Recurrent Glioblastoma

INTRODUCTION: Chimeric antigen receptor (CAR) T cells represent a promising approach to cancer and have proven efficacy against hematological malignancies, for which they have become the standard of care. However, the use of CAR T cells in solid tumors has been limited. METHODS: This is a nonrandomized, open-label, single-site Phase I clinical trial. Three patients with EGFRvIII-positive recurrent glioblastoma were enrolled in a safety run-in cohort. Patients were treated with 10 million CARv3-TEAM-E T cells and monitored for toxic effects. Cerebrospinal fluid (CSF) and blood were sampled longitudinally and subjected to correlative analyses. RESULTS: No dose-limiting toxic effects were noted. Radiographic tumor regression occurred in all three patients within days after treatment, but this response was transient in two of the patients. Tumor regression correlated with decreased detection of antigen-specific RNA derived from extracellular vesicles (EVs) in both CSF and peripheral blood. CONCLUSIONS: Early data suggest safety and anti-tumor activity of CARv3-TEAM-E T cells in recurrent glioblastoma. EV-based liquid biopsy may assist in monitoring response to cell therapy. Ongoing enrollment has been modified to enhance durability using lymphodepletive chemotherapy. Additional arms will evaluate this approach in the setting of EGFRvIII-negative tumors and newly-diagnosed disease.