Patients with a newly diagnosed glioblastoma multiforme (GBM) brain tumor will be able to enroll soon in a Phase 1b/2a clinical trial of a triple-combination immunotherapy for the cancer.
INO-5401 encodes the antigens for the WT1, hTERT, and PSMA proteins, which are expressed at high levels in several cancers. An antigen is a toxin or other foreign substance that triggers an immune response in the body, especially the production of antibodies. Expression is the process by which information from a gene is used to create a functional product like a protein.
While INO-5401 encodes for antigens, INO-9012 encodes for the interleukin (IL)-2 protein, which triggers the activation and expansion of immune cells known as T-cells.
“I am a strong believer in this combination regimen approach in immuno-oncology,” Dr. J. Joseph Kim, Inovio’s president and chief executive officer, said in a news release. He said the approach uses Inovio immunotherapies to generate killer T-cells that can turn cold tumors into hot tumors, and checkpoint inhibitors to block T-cell suppression.
“This [combo-therapy] step with INO-5401 is very important for us in 2017, as we believe INO-5401 has the potential to be a powerful cancer immunotherapeutic in combination with promising checkpoint inhibitors such as Regeneron’s REGN2810,” Kim said. “We look forward to investigating its potential for GBM and multiple other challenging cancers.”
“Regeneron’s approach to oncology includes evaluating the combination of innovative therapies that act on diverse pathways and targets,” said Dr. Israel Lowy, a Regeneron vice president. “Using our PD-1 inhibitor as a therapeutic backbone alongside Inovio’s T-cell-generating therapies offers a new path for exploration and heightens the potential to develop new, desperately needed treatment options for patients.”
The open-label Phase 1b/2a trial, expected to begin this year, will involve 50 patients at 30 U.S. sites. The study’s primary goals are to see if the triple-combo therapy is safe and effective. Secondary measures of the combo’s success will be patients’ survival until the disease progresses, overall survival, and how well the combo can trigger an immune response.
Under terms of the clinical trial agreement, Inovio will conduct and fund the study, and Regeneron will supply the REGN2810 that’s used. The companies will do a joint evaluation of the study’s results.
GBM is the most aggressive form of brain cancer, and has a very poor prognosis. Although regulators approved a number of therapies for it in the past 10 years, median overall survival is only 15 months, and only 3 percent of patients live beyond five years.
“The unmet need for effective therapies in GBM remains extremely high,” said Dr. David Reardon, a Harvard Medical School professor who is also clinical director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute. “Certain immune checkpoint inhibitors have shown efficacy in certain cancers, but evidence increasingly suggests that the benefit of checkpoint inhibitors can be enhanced when used in combination with therapies that generate T-cells.
“Inovio has an innovative immunotherapy platform which has shown the ability to generate antigen-specific T-cells in disease areas including cancer,” Reardon added. “We look forward to exploring the potential of combining a T-cell-generating immunotherapy encoding multiple antigens with REGN2810, a PD-1 checkpoint inhibitor.”