Positive interm results of a T cell-activating immunotherapy (INO-5401; Inovio Pharmaceuticals, Plymouth Meeting, PA) were seen in a phase 2 study (NCT03491683) of a T cell-activating immunotherapy for treatment of newly diagnosed glioblastoma multiforme (GBM) combining Inovio's INO-5401, a T cell-activating immunotherapy encoding for three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, an immune activator encoding IL-12, in combination with Libtayo (cemiplimab)(Libtayo; Regeneron and Sanofi Genzyme,Tarrytown, NY).
Key interim data from the 52 participants clinical trial showed that 80% (16 of 20) of participants MGMT gene promoter methylated (GBM) and 75% (24 of 32) of unmethylated participants were progression free at 6 months (PFS6) measured from the time of their 1st dose, substantially exceeding historical standard-of-care data.
This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested a safety profile consistent with that of Libtayo and Inovio’s platform technology. The majority of participants tested had a T cell-immune response to 1 or more tumor-associated antigens encoded by INO-5401. Immune responses to all 3 tumor-associated antigens were demonstrated in this study. Inovio plans to report 12- and 18-month overall survival data next year.
Dr. David Reardon, MD, coordinating principal investigator of the study and the clinical director for Neuro-Oncology at the Dana-Farber Cancer Institute, said, “This innovative trial provides promising information that the combination of INO-5401 plus INO-9012, a T cell-promoting therapy, combined with Libtayo, a checkpoint inhibitor, may provide clinically meaningful benefit in this very difficult to treat disease.”
Dr. J. Joseph Kim, Inovio's president & CEO, said, "Our new data demonstrate the potential of our immunotherapies utilizing tumor-associated antigens in cancer treatments. Our goal in this GBM trial is to increase progression-free and overall survival of patients facing a disease where neither the standard of care nor clinical outcomes have significantly advanced in decades. Previously, other checkpoint inhibitor treatment alone in GBM trials did not show any meaningful clinical benefit over standard of care. However, the addition of INO-5401 and its ability to generate antigen-specific T cells demonstrated early efficacy signals in progression-free survival. We look forward to reporting additional data including overall survival at months 12 and 18 from the trial in the coming year.”
James Geyer, MD, and Thomas Patton, MD
Ganesh M. Babulal, PhD, OTD, and Catherine M. Roe, PhD
Cyrus A. Raji, MD, PhD; Somayeh Meysami, MD; and Mario F. Mendez, MD, PhD