Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment.
Journal of experimental & clinical cancer research : CR
california; jwci; sjci; pni; Autologous tumor antigens; Dendritic cell vaccine; Glioblastoma; Survival; Adolescent; Adult; Aged; Humans; Middle Aged; Young Adult; Antineoplastic Agents, Alkylating; Brain Neoplasms; Dendritic Cells; Glioblastoma; Seizures; Temozolomide; Treatment Outcome; Vaccines
BACKGROUND: Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Events (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 concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (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 μg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) 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. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (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.
Bota, Daniela A; Taylor, Thomas H; Piccioni, David E; Duma, Christopher M; LaRocca, Renato V; Kesari, Santosh; Carrillo, Jose; Abedi, Mehrdad; Aiken, Robert D; Hsu, Frank P K; Kong, Xiao-Tang; Hsieh, Candace; Bota, Peter G; Nistor, Gabriel I; Keirstead, Hans S; and Dillman, Robert O, "Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment." (2022). Articles, Abstracts, and Reports. 6783.