Data from the multi-center Phase 2 clinical trial of AV-GBM-1 (AIVITA Biomedical; NCT03400917), a personalized cancer vaccine, in patients 18 years or older with newly diagnosed glioblastoma (GBM) demonstrated a considerable increase in progression-free survival (PFS).

AV-GBM-1 is a novel immunotherapy consisting of autologous dendritic cells loaded with autologous tumor neoantigens derived from self-renewing tumor-initiating cells isolated from tumors after routine surgical debulking. The treatment is administered to patients via subcutaneous injection. The treatment is uniquely pan-antigenic, targeting multiple antigens, including all neoantigens, from autologous tumor-initiating cells that are responsible for the tumor growth.

The single-arm, open-label study enrolled patients with newly diagnosed glioblastoma (GBM) with the intent to treat them with an autologous dendritic cell vaccine consisting of autologous dendritic cells loaded with autologous tumor-associated antigens.

Patients eligible for treatment recovered from surgery and were scheduled to begin concurrent chemotherapy and radiation therapy (CT/RT), included patients for whom an autologous tumor cell line had been established, or had a KPS of > 70, or had undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained to generate dendritic cells (DC).

Analyses
The analysis if the trial data focused on the 57 Phase 2 patients who received eight doses of AV-GBM-1 over approximately six months. At the time of the analysis, surviving patients had completed therapy and had been followed between 10.1 and 27.6 months from enrollment.

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The median length of PFS was 10.4 months (95% confidence interval; 8.6 to 11.7 months), an improvement of approximately 50% compared to a median PFS of 6.9 months (95% confidence interval; 5.8 to 8.2 months) in the landmark STUPP study that established the standard of care for patients with newly diagnosed GBM. [1]

This represents a 42% reduction in the risk of progression or death at 6.9 months. Median survival has not been reached and will be assessed after the final patient has a minimum follow up of 15 months. Overall, the treatment was well tolerated. There were 54 serious adverse events among 28 of 57 patients but none were attributed to the vaccine.

Principal investigator Daniela A. Bota, M.D., Ph.D., Director, University of California, Irvine (UCI) Alpha Stem Cell Clinical and medical director, UCI Health Comprehensive Brain Tumor Program.

“The potential for AV-GBM-1 to significantly improve PFS in newly diagnosed GBM patients over and above current standard of care is very encouraging,” said Robert O. Dillman, M.D., chief medical officer of AIVITA.

“We look forward to confirming this benefit in a randomized Phase 3 multi-center trial,” Dillman added.

“This milestone is an encouraging first step in the fight against GBM, a disease that has a devastating impact on patients and their families,” said study principal investigator Daniela A. Bota, M.D., Ph.D., Director, University of California, Irvine (UCI) Alpha Stem Cell Clinical and medical director, UCI Health Comprehensive Brain Tumor Program.

Incidence and occurrence
Glioblastoma, also referred to as a grade IV astrocytoma, has an incidence of 3.21 per 100,000 population. The median age of diagnosis of the disease, which is more common in men than women, is 64 years. Survival is poor with approximately 40% survival in the first year post-diagnosis and 17% in the second year. Glioblastoma is a fast-growing and aggressive brain tumor and invades the nearby brain tissue, but generally does not spread to distant organs. The disease can arise in the brain de novo or evolve from lower-grade astrocytoma. In adults, glioblastoma generally occurs in the cerebral hemispheres, especially in the frontal and temporal lobes of the brain. The disease is a devastating brain cancer that can result in death in six months or less, if untreated. [2]

Note
World Health Organization (WHO) Grade IV glioma, Grade IV anaplastic astrocytoma, glioblastoma or gliosarcoma, glioblastoma multiforme (GBM)

Clinical trials
Autologous Dendritic Cells Loaded With Autologous Tumor Associated Antigens for Treatment of Newly Diagnosed Glioblastoma – NCT03400917)

Reference
[1] Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. PMID: 15758009.
[2] Wirsching HG, Galanis E, Weller M. Glioblastoma. Handb Clin Neurol. 2016;134:381-97. doi: 10.1016/B978-0-12-802997-8.00023-2. PMID: 26948367.

Featured image: Glioblastoma. Photo courtesy: © 2021 AIVITA Biomedical. Used with permission.

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