A novel combination of two experimental cancer immunotherapy agents along with an immune checkpoint blocker elicited robust immune responses in patients with newly diagnosed glioblastoma brain tumors, according to a presentation of interim, 2-year follow-up clinical trial data given by David Reardon, MD, at the 2022 ASCO Annual Meeting (Abstract 2004). The combination therapy also demonstrated an acceptable risk/benefit profile.
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 well tolerated, said Dr. Reardon, Clinical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute. Dr. Reardon was also the coordinating principal investigator of the GMB-001 clinical trial.
David Reardon, MD
GMB-001
The trial is sponsored by the biotech company INOVIO, which has designed two agents, or “DNA medicines,” aimed at stimulating immune T cells in the body to target specific antigens that are highly expressed in glioblastoma tumors. These two agents, called INO-5401 and INO-9012, were given as an intramuscular injection to patients who have had surgery to remove as much tumor 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 tumor. These were given along with cemiplimab, a PD-1 inhibitor.
GMB-001 was a phase I/II, single arm, two-cohort (A: unmethylated MGMT and B: methylated MGMT) study. Fifty-two patients were enrolled: 32 into cohort A and 20 into cohort B (35% women; median age = 60 years [range = 19–78 years]).
The median overall survival rate of 17.9 months in cohort A showed “modest improvement” compared to historical medians of 14 to 16 months in patients with the less-favorable unmethylated MGMT promoter status, and the median overall survival rate of 32.5 months in cohort B compared to historical 23- to 25-month median survival in patients with the more-favorable methylated MGMT status.
The adverse event profile was consistent with known single-agent events; most events were ≤ grade 2 and no related events were grade ≥ 4.
“These data are encouraging,” said Dr. 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 tumor vaccine strategy plus PD-1 checkpoint blockade in newly diagnosed patients with glioblastoma.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
