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April 13, 2020 06:22pm
By Lisa Astor
An autologous dendritic cell vaccine consisting of autologous dendritic cells loaded with autologous tumor-associated antigens demonstrated promising survival findings in patients with newly diagnosed glioblastoma, according to updated data from a year-end analysis of an ongoing phase II clinical trial.
A vaccine consisting of autologous dendritic cells loaded with autologous tumor-associated antigens (AV-GBM-1) demonstrated promising survival findings in patients with newly diagnosed glioblastoma, according to updated data from a year-end analysis of an ongoing phase II clinical trial (NCT03400917). These data were announced in a press release by AIVITA Biomedical, Inc.1
At both 12 and 15 months, the overall survival (OS) rate was 76% in patients with newly diagnosed glioblastoma who were treated with AV-GBM-1. The study is a single-arm trial, but AIVITA included data from a control cohort of individuals with newly diagnosed glioblastoma who received standard of care treatment (n = 287). In this patient population, OS was 61% at 12 months and 48% at 15 months with standard therapy.
“Although treatment and monitoring of patients is ongoing, we are encouraged by these interim results. We completed accrual to the trial ahead of schedule, thanks to the engagement of our clinical site principal investigators and a truly outstanding manufacturing success rate at AIVITA,” Robert O. Dillman, MD, chief medical officer of AIVITA, said in a press release.
At the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting, interim results demonstrated survival of 96% at 6 months and 91% at 12 months with AV-GBM-1. The majority of patients in the study also had an appropriate immune response, as well as a decrease in tumor biomarkers.2
According to the findings presented at SITC, 46 out of 48 patients had established cell lines successfully, and dendritic cells were produced for 41 out of 42 patients. Thirty-eight patients were enrolled as of the end of October 2019, and 31 patients had started therapy. Twelve patients had completed all 8 doses.
Enrollment for the single-arm, open-label study is complete with 55 patients enrolled across 8 trial sites, including sites in California, Kentucky, and New Jersey. In the updated survival analysis, 50 patients receiving AV-GBM-1 were analyzed.1
The primary end point of the trial is OS. Secondary end points include progression-free survival (PFS) from date of enrollment; OS/PFS from date of diagnosis; and OS/PFS from date of enrollment based on Karnofsky Performance Status (KPS), age, and extent of surgical resection. Patients receive AV-GBM-1 as an adjunctive therapy following primary surgery and concurrent chemoradiation.
To be eligible, patients must have recovered from surgery and be ready for concurrent chemotherapy and radiation therapy, an established autologous tumor cell line, a KPS of greater than 70, and undergone successful leukapheresis from which peripheral blood mononuclear cells were obtained to be used for generation of the dendritic cells. Patients are excluded from the study if they have recurrent glioblastoma.
The agent consists of autologous dendritic cells that are loaded with autologous tumor antigens from self-renewing tumor-initiating cells. AV-GBM-1 is given in a series of subcutaneous injections as an adjunctive therapy. The unique pan-antigenic therapy targets multiple antigens on autologous tumor-initiating cells that are responsible for the rapid growth of disease, as well as resistance to standard treatments.
Two additional studies of AV-GBM-1 remain ongoing as well, which includes an open-label single-arm phase Ib trial of AV-GBM-1 with PD-1 inhibition in patients with melanoma (NCT03743298) and a double-blind phase II trial of AV-GBM-1 versus autologous monocytes in patients with advanced epithelial ovarian cancer (NCT02033616). All 3 trials remain ongoing. The melanoma study has not yet begun recruitment, but the ovarian cancer trial has been ongoing since 2017 with a target enrollment of 99 patients.
In patients with metastatic melanoma, the novel immunotherapy led to a 2-year survival rate of 72% and a 5-year survival rate of 54% in a past clinical trial. The company is seeking conditional commercial approval of its treatment for melanoma in Japan based on past data, while the phase II clinical trials in ovarian cancer and glioblastoma remain ongoing for newly diagnosed patients.
In the phase Ib study in melanoma, investigators will evaluate the safety of combining this novel therapy with an antiPD-1 monoclonal antibody in patients with measurable metastatic melanoma. To be included in the study, patients must have an established cell line, undergone leukapheresis in which sufficient monocytes were obtained, an ECOG performance status of 0 or 1, and never received treatment for metastatic melanoma or previous enzymatic inhibition of the BRAF/MEK pathway.
The clinical trial evaluating AV-GBM-1 in ovarian cancer will randomize patients 2:1 to either AV-GBM-1 or autologous monocytes. Eligibility criteria for this trial are similar to that of the melanoma trial, but patients must also have completed primary therapy prior to the study. Patients with recurrent ovarian cancer are excluded.