November 17, 2020 - AV-GBM-1, a personalized cancer vaccine, demonstrated an improvement in progression-free survival in patients with newly diagnosed glioblastoma.
AV-GBM-1, a personalized cancer vaccine, demonstrated an improvement in progression-free survival (PFS) in patients with newly diagnosed glioblastoma, according to data from a phase 2 trial (NCT03400917).1
Results presented during the 2020 SITC Annual Meeting showed that the vaccine resulted in a PFS rate of 69% at 7 months, which favorably compares with the historical rate of 50% at this time point.2 The median PFS was 10.0 months (95% CI, 8.5-11.5) with the vaccine versus 6.9 months (95% CI, 5.8-8.2) in the landmark study that had established the standard of care for this patient population. This translated to a 38% reduction in the risk of progression or death at 6.9 months of treatment, according to AIVITA Biomedical Inc.
Moreover, the overall survival (OS) rate at 12 months was 72% with AV-GBM-1, which also compares favorably with the historical rate of 61%.
“The improvement in [patients with] glioblastoma who were treated with AV-GBM-1, compared to studies with the standard of care, is a very promising indication that our therapy confers benefit to patients in need,” Robert O. Dillman, MD, chief medical officer, of AIVITA Biomedical, Inc, stated in a press release.
Standard approaches for patients with primary glioblastoma are linked with poor survival outcomes. Investigators hypothesized that adjunctive therapy with patient-specific vaccines could help to improve these outcomes in patients by boosting immune response. AV-GMB-1 is made of autologous dendritic cells that are comprised of autologous tumor antigens from self-renewing tumor-initiating cells.
In the single-arm, phase 2 trial, a total of 57 patients were scheduled to receive up to 8 doses of AV-GBM-1 over the course of 6 months. At the time of the analysis, patients had completed treatment and had been followed for further analysis between 7.2 months and 24.2 months.
Patients were enrolled to the trial after they recovered from surgery and before they began treatment with concurrent temozolomide chemotherapy and radiation. To be eligible for participation, patients had to have a diagnosis of primary glioblastoma, be 70 years of age or younger at the time of tumor resection, have a successful cell culture of cancer cells in serum-free media, have acceptable monocyte collection by leukapheresis, and a Karnofsky performance score (KPS) of 70 or greater following surgical recovery.
Investigators utilized interleukin-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) to produce dendritic cells from peripheral blood monocytes. Dendritic cells were generated with autologous tumor antigens from the lysate of the cancer cells to manufacture each patient-specific vaccine. Patients began treatment after they recovered from concurrent treatment with chemotherapy and radiation. With each vaccine dose given, GM-CSF was also given at 500 mcg at the time of the injection on weeks 1, 2, 3, 8, 12, 16, 20, and 24.
Investigators collected tumors between August 18, 2018 and January 15, 2020. Patients were enrolled for treatment between October 3, 2018, and February 27, 2020. A total of 80 tumors were received and 71 of 73 were determined to have successful cell lines. Seven patients withdrew while the cell line was in progress. A total of 65 leukapheresis procedures were conducted, but 6 patients withdrew prior to this. Sixty patients were enrolled to the intent-to-treat population. Three patients withdrew before beginning treatment.
The key objectives of the trial include confirmation of the feasibility of producing patient-specific vaccines, the safety of administering these vaccines, survival from the date of enrollment, PFS from date of enrollment, and survival from the date of diagnostic surgical resection.
The median age of study participants was 59 years and the majority, or 70%, were male. Moreover, 72% were white, 17% were Hispanic, 3% were Black, and 2% were Asian. A little more than half of patients, or 52%, did not have MGMT methylation, while 22% did; for 27% of patients, this information was unknown. Twelve percent of patients had tumors that harbored an IDH mutation. Forty-two percent of patients had a KPS of 90, 28% had a score of 80, 23% had a score of 70, and 7% had a score of 100.
Fifty-seven patients received treatment. Of these patients, 39 received all 8 doses, 2 patients completed 7 doses, 5 received 6 doses, 2 received 4 doses, 5 received 3 doses, and 3 completed 2 doses.
Regarding safety, the vaccine was found to be well tolerated. The most commonly reported toxicity was local injection site reactions. Notably, no study participants stopped treatment because of adverse effects. Fifty-four serious toxicities were observed among 28 patients, although none of these effects were determined to be associated with the vaccine.
Many of these toxicities were related to the central nervous system; 10 patients reported falls and/or focal weakness and 3 experienced headaches and/or cerebral edema. One death was reported; this occurred after 2 injections with the vaccine. The patient fell at home, refused to go to the hospital, and died 2 days later.
“This is a major victory against glioblastoma, a devastating disease that has evaded treatment for far too long,” Hans S. Keirstead, PhD, chairman and chief executive officer of AIVITA, added in the release. “We now have excellent results from phase 2 clinical studies in both melanoma and glioblastoma, underscoring the tremendous potential of this personalized cancer immunotherapy.”
The vaccine is under examination in 3 clinical trials in patients with ovarian cancer, melanoma, and glioblastoma. AIVITA announced that they are working on obtaining a conditional commercial approval in Japan for its melanoma treatment.