Phase 2 Study of AV-GBM-1 (a Tumor-initiating Cell Targeted Dendritic Cell Vaccine) in Newly Diagnosed Glioblastoma Patients: Safety and Efficacy Assessment

Abstract Background Vaccine immunotherapy may improve survival in GBM. A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing AV-GBM-1, (2) AE associated with AV-GBM-1 administration, and (3) survival. Methods Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting RT/TMZ with ITT after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous TICs. Eligible patients were adults (18 to 70 years old) with a KPS of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 mg of granulocyte-macrophage colony-stimulating factor before every subcutaneous (s.c.) administration. Results Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. mPFS and mOS from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year OS is 27%. Conclusions: AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted. Trial Registration: NCT, NCT03400917, Registered 10 January 2018, https://clinicaltrials.gov/ct2/show/NCT03400917?term=NCT03400917&draw=2&rank=1