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Clinical Trial
. 2022 Dec 14;41(1):344.
doi: 10.1186/s13046-022-02552-6.

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment

Daniela A Bota  1 , Thomas H Taylor  2   3 , David E Piccioni  4 , Christopher M Duma  5 , Renato V LaRocca  6 , Santosh Kesari  7 , Jose A Carrillo  5   7 , Mehrdad Abedi  8 , Robert D Aiken  9 , Frank P K Hsu  2 , Xiao-Tang Kong  2 , Candace Hsieh  10 , Peter G Bota  10   11 , Gabriel I Nistor  10 , Hans S Keirstead  10 , Robert O Dillman  10
Affiliations
Clinical Trial

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment

Daniela A Bota et al. J Exp Clin Cancer Res. .

Abstract

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.

Keywords: Autologous tumor antigens; Dendritic cell vaccine; Glioblastoma; Survival.

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Conflict of interest statement

Authors CH, PGB, GIN, HK, PGB and ROD are/were affiliated with Aivita Medical, the sponsor of this clinical trial.

Figures

Fig. 1
Fig. 1
Flow diagram of AV-GBM-1 nGBM trial (Reformatted)
Fig. 2
Fig. 2
OS and PFS from intent-to-treat enrollment
See this image and copyright information in PMC

References

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