In a phase 1/2 clinical trial (NCT03491683), 85% (44 out of 52) of individuals newly diagnosed with glioblastoma multiforme (GBM) who received 2 new immunotherapeutic agents (INO-5401, INO-9012, Inovio Pharmaceuticals, Plymouth Meeting, PA) and cemiplimab (Libtayo, Inovio Pharmaceuticals), have survived for 12 months or more. The median (50%) overall survival rate with standard of care therapy for GBM, which includes radiation and chemotherapy (temozolomide: TMZ), is 15 to 22 months.This data will be featured at an oral poster presentation at the ASCO 2020 Virtual Scientific Program, May 29 to 31, 2020.
Of participants with MGMT promoter unmethylated tumors and methylated tumors, respectively, 84.4% (27/32) and 85% (17/20) were alive at 12 months. This clinical result is coupled with a robust immunological response to all 3 cancer antigens in immunotherapy INO-5401, including human telomerase (hTERT), Wilms tumor-1 (WT-1), and prostate-specific membrane antigen (PSMA). Activated cytotoxic T cells directed towards these cancer antigens commonly expressed on GBM tumors were detected in all participants tested to date and continue to support the immunogenic potential of these investigational therapies. The immunotherapeutic agent was safe and well-tolerated when given not only with radiation and temozolamide (TMZ) but also with PD-1 inhibition with cemiplimab, which is being jointly developed by Regeneron and Sanofi. These results are also being presented in a virtual format at the 2020 Annual ASCO meeting.
Dr. David Reardon, clinical director, Center for Neuro-Oncology of Dana-Farber Cancer Institute and coordinating principal investigator of the trial said, "Although these data are preliminary, and follow-up remains early, this novel combination of a cancer antigen-specific, T-cell generating DNA medicine with a PD-1 inhibitor is exciting and may overcome more than 20 years of a standard of care that has proven suboptimal for our patients with GBM. A tolerable, new combination of medicines utilizing a novel mechanism of action, such as that provided by INO-5401 and INO-9012 with cemiplimab, is very welcome for this hard-to-treat brain cancer, especially when shown to be tolerable with standards such as radiation and chemotherapy, and when demonstrating the immunogenicity seen in the study."
Dr. J. Joseph Kim, Inovio's president & chief executive officer, said, "While we recognize these data are early, we are very excited to see robust immunogenicity and the potential for extending survival, coupled with a clear ability to be able to combine not only with the standard of care, but with a checkpoint inhibitor, cemiplimab. Where others have failed with single-agent checkpoint inhibition in GBM, our DNA medicine combined with cemiplimab and standard of care has demonstrated clear immunogenicity and the potential to extend overall survival."
David Z. Rose, MD
F. Stephen Benesh, MD, and Shruti P. Agnihotri, MD
Michelle L. Dougherty, MD, FAES, FAAN