April 12, 2021
Treovir, an immuno-oncology company that is developing and plans to commercialize G207 for recurrent glioblastoma in children, announced today that G207, an oncolytic HSV immunotherapy, was well tolerated with evidence of clinical effectiveness in a phase 1 study of 12 pediatric patients with recurrent high-grade glioma.
Data from the phase 1 study (NCT02457845) are being presented by Gregory Friedman, M.D., professor in the Department of Pediatrics at the University of Alabama at Birmingham, during Week 1 of the virtual AACR Annual Meeting 2021, held April 10-15. Data from this trial have been published in the New England Journal of Medicine.
In Phase 1 dose-escalation study, 12 pediatric patients 7 to 18 years of age with progressive high-grade glioma received an infusion of G207 alone or G207 in combination with radiation. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators and only 20 grade 1 adverse events were possibly related to G207.
Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4). The overall survival rate was more than double the typical survival rate for children with high-grade glioma. Some 36 percent of the patients thus far have survived longer than 18 months, surpassing the expected survival for newly diagnosed children with high-grade glioma. Additionally, G207 markedly increased the number of tumor-infiltrating lymphocytes for at least nine months after infusion effectively turning immunologically “cold” tumors “hot”.
Gregory Friedman, M.D., Principal Investigator of the study, said, “This is the first study utilizing delivery of a viral immunotherapy directly into brain tumors in children and the results indicate that G207 can be delivered safely into tumors located in all areas of the cerebrum in children. The key findings thus far are that the approach is safe and well tolerated, and the preliminary evidence of efficacy is very promising.”
G207 is an oncolytic HSV engineered to infect only tumor cells. When infused into a tumor, the virus enters the tumor cells and replicates and kills the cells. In the process, G207 releases viral progeny that infect and kill nearby tumor cells. Furthermore, as demonstrated in the Phase 1 study for the first time, G207 induces a strong local immune response to harness the body’s immune system to further fight against the tumor cells.
“We are enthusiastic that the Phase 1 results appear to support the use of G207 as a safe and potentially effective therapy to treat pediatric high-grade gliomas,” said Michael Christini, CEO of Treovir. “There are no approved therapies to treat these types of lethal tumors and it is our goal to develop G207 for glioma and other childhood brain cancers.”
In collaboration with Dr. Friedman and the Pediatric Brain Tumor Consortium, Treovir is in the late stages of planning its Phase 2 clinical trial for G207 in recurrent high grade glioma (NCT 04482933). The Phase 2 trial is expected to start later in 2021. Additionally, G207 is being studied at UAB and Children’s of Alabama in recurrent pediatric brain tumors, including medulloblastoma, which arise in the cerebellum, the most common location for pediatric tumors to arise. (NCT 03911388)
“It is our goal that the Phase 2 study will support market approval of G207 to treat pediatric recurrent high-grade gliomas and our company’s mission is clear: We want to commercialize G207 and provide hope to the children and families who currently have no effective therapeutic options,” stated Mr. Christini.
Brain tumors are the most common solid tumor in children, and aggressive types like glioblastoma have an extremely low survival rate: as low as 10% five years after diagnosis. Malignant high-grade glioma accounts for 8 to 10% of pediatric brain tumors and survival rates have not improved in 30 years. The median life expectancy of recurrent high-grade glioma is only 5.6 months.
The study was supported by the US FDA Orphan Products Clinical Trials Grants Program, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, and the Kaul Pediatric Research Institute. Dr. Friedman has no financial or equity interest in Treovir and was not paid by Treovir for the Phase 1 study.