INOVIO (NASDAQ:INO) today announced that 85 percent (44 out of 52) of patients newly diagnosed with the deadly brain cancer glioblastoma multiforme (GBM) who received the company's DNA medicine INO-5401, in combination with INO-9012 and PD-1 inhibitor Libtayo® (cemiplimab), were alive for at least 12 months or more (overall survival at 12 months: OS12) following treatment. These data will be featured at an oral poster presentation at the ASCO 2020 Virtual Scientific Program, May 29-31, 2020.
GBM is the most common and aggressive type of brain cancer. Currently, the median overall survival with standard of care therapy, which includes radiation and chemotherapy (temozolomide: TMZ), is approximately 15 to 22 months.
The Phase 1/2 clinical trial demonstrated that 84.4% percent (27 of 32) of patients with MGMT promoter unmethylated tumors, and 85% (17 of 20) of patients with MGMT promoter methylated tumors were alive at 12 months. This promising clinical result is coupled with a robust immunological response to all three cancer antigens in 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 patients tested to date and continue to support the immunogenic potential of INOVIO's DNA medicines. Importantly, INO-5401 + INO-9012 was safe and well-tolerated when given not only with radiation and TMZ, but also with PD-1 inhibition with Libtayo, which is being jointly developed by Regeneron and Sanofi. These results are being presented in a virtual format at the 2020 Annual ASCO meeting (Abstract #2514).
Dr. David Reardon, Clinical Director, Center for Neuro-Oncology of Dana-Farber Cancer Institute and coordinating principal investigator of GBM-001 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 sub-optimal 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 GBM-001 study."
Dr. J. Joseph Kim, INOVIO's President & CEO, 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, Libtayo. Where others have failed with single-agent checkpoint inhibition in GBM, our DNA medicine combined with Libtayo and standard of care has demonstrated clear immunogenicity and the potential to extend overall survival."
In a previous announcement, INOVIO reported key interim data from the 52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter methylated patients and 75% (24 of 32) unmethylated patients were progression-free at six months (PFS6) measured from the time of their first dose, 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 an acceptable safety profile consistent with that of Libtayo and INOVIO's platform technology. The majority of patients tested had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401. Immune responses to all three tumor-associated antigens were demonstrated in this study. INOVIO plans to report 18-month overall survival data later this year.
The trial was designed to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There are two cohorts in this trial. Cohort A includes 32 participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B includes 20 participants with a tumor with a MGMT methylated promoter. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and temozolomide (TMZ). Interim data presented here and at SITC was obtained as of October 2019 and overall survival data at 18 months is expected in Q4 2020. For more information of the clinical study, see www.clinicaltrials.gov, identifier NCT03491683.
Poster Discussion Session: Central Nervous System Tumors
The ASCO 2020 Virtual Scientific Program runs from May 29 -31.