ASCO 2022: Immunotherapy drug combination is safe with promising results in glioblastoma

27 May 2022
ASCO 2022: Immunotherapy drug combination is safe with promising results in glioblastoma

A novel combination of two experimental cancer immunotherapy agents along with an immune checkpoint blocker is yielding promising results in patients with newly diagnosed glioblastoma brain tumours, according to a presentation of interim, two-year follow-up clinical trial data by a Dana-Farber neuro-oncologist at the ASCO meeting.

The data from the phase I/II open-label GBM-001 trial found that “a significant percentage of patients had a robust immune response” in the peripheral blood stream and the drug combination was very well tolerated, said David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber and coordinating principal investigator of the GMB-001 clinical trial that includes 52 patients with the highly aggressive and lethal glioblastoma brain tumour.

Moreover, median survival of 17.9 months shows “modest improvement” compared to historical medians of 14 to 16-months in patients with the less-favourable unmethylated MGMT promoter status, and a median survival of 32.5 months compared to historical 23 to 25-month median survival in patients with the more-favourable methylated MGMT status.

“These data are encouraging,” said Reardon, “and they highlight that combination immunotherapy for this disease may be an effective strategy where single agent immunotherapy has not worked very well. This is one of the first trials to combine a tumour vaccine strategy plus PD-1 checkpoint blockade in newly diagnosed glioblastoma patients.”

The trial is sponsored by the biotech company INOVIO which has designed two agents, or “DNA medicines” as it calls them, aimed at stimulating immune T cells in the body to target specific antigens that are highly expressed in glioblastoma tumours.

These two agents, called INO-5401 and INO-9012, are given as an intramuscular injection to patients who have had surgery to remove as much tumour as possible. INO-5401 targets three glioblastoma antigens and INO-9012 is a synthetic DNA plasmid that codes for IL-12, a T cell immune activator, to help rev up the immune response against the tumour.

These are given along with cemiplimab, a PD-1 inhibitor which aims to release the molecular brakes cancers use to suppress the immune response.

Source: Dana-Farber Cancer Institute