IMCT-15PILOT STUDY OF T CELLS REDIRECTED TO EGFRvIII WITH A CHIMERIC ANTIGEN RECEPTOR IN PATIENTS WITH EGFRvIII+ GLIOBLASTOMA

We have initiated a first-in-human pilot study of intravenous delivery of autologous T cells re-directed to the EGFR variant III mutation by means of a lentiviral vector encoding a chimeric antigen receptor (CAR). Patients with recurrent or incompletely resected glioblastoma (GBM) have their tumors screened for the presence of the EGFRvIII mutation by a next-generation sequencing based assay. Eligible patients undergo leukapheresis for collection of autologous T cells, which are then manufactured to form CART-EGFRvIII T cell products. We report preliminary results on the first six patients we have treated. We targeted a challenging subset of GBM patients, with multi-focal recurrent, residual, progressive disease refractory to standard and experimental therapies, including chemotherapy, radiation, bevacizumab and prior immunotherapy. To date, we have found that infusion of CART-EGFRvIII cells is safe, without evidence of off-tumor toxicity such as cross-reactivity to wild type EGFR. No clinical or laboratory signs of systemic cytokine release syndrome have been observed. One patient developed a seizure and non-convulsive status epilepticus nine days after CART-EGFRvIII infusion. Seizures resolved with anti-epileptic medications, and the patient was treated with steroids and anti-IL6 cytokine therapy. All patients have had significant expansion of CART-EGFRvIII cells as measured by flow cytometry and quantitative PCR in peripheral blood samples, despite the use of steroids in two patients. In one of two patients who had operative resection of presumed residual tumor, pathologic evaluation demonstrated inflammation, T cell infiltration, and EGFRvIII antigen loss. In total, two of six heavily pretreated patients are clinically stable three months post-CART infusion. These findings provide preliminary evidence that CART-EGFRvIII cells are safe, without evidence of off-target toxicity and without evidence of cytokine release syndrome, and that these are active T cell products that expand in the blood.