This is a rapidly fatal form of brain cancer. Among historical control patients, the median overall survival was only 5.3 months.
The new results show a median overall survival of 12.2 months.
They come from a phase 1 trial conducted in 12 patients aged 7-18 years who had high-grade gliomas. All of the patients received the experimental therapy, dubbed G207, which was infused directly into the brain tumors.
“In our secondary objectives, we saw promising overall survival data ... [and] we saw that G207 turned immunologically ‘cold’ tumors to ‘hot,’ ” said lead investigator Gregory K. Friedman, MD, from the University of Alabama at Birmingham.
Dr. Friedman presented the new data at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT018). The study was also published simultaneously online in the New England Journal of Medicine.
Although the number of patients in the study was small, the data from this early trial look promising, commented Howard Kaufman, MD, director of the Oncolytic Virus Research Laboratory at Massachusetts General Hospital, Boston, who was not involved in the study.
“This is just a horrendous disease that hasn’t really responded to anything, so seeing some signs of benefit as well as a pretty tolerable safety profile is a very important observation that I think merits further investigation,” he said in an interview.
Engineered virus
G207 is an oncolytic form of HSV-1 created through genetic engineering in which a neurovirulence gene was deleted and viral nucleotide reductase was disabled. The engineered mutations prevent HSV-1 from infecting normal cells while allowing the virus to replicate in tumor cells.
The oncolytic virus product can be inoculated directly into tumors to circumvent the blood-brain barrier, and it preferentially infects neural tissue, making it ideal for treating brain tumors, the investigators explain.
One example of this type of product is already on the market. Talimogene laherparepvec is an oncolytic HSV-1 therapy that was approved in 2015 by the Food and Drug Administration for local treatment (i.e., injection directly into the skin lesion) of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that recurs after initial surgery.
In their article, Dr. Friedman and colleagues summarized some of the data with G207 that “provided a strong rationale for conducting a trial involving children and adolescents.
“In addition to infecting and lysing tumor cells directly, G207 can reverse tumor immune evasion, increase cross-presentation of tumor antigens, and promote an antitumor immune response even in the absence of virus permissivity,” they wrote. “A single radiation dose enhances G207 efficacy in animal models by increasing viral replication and spread.”
In preclinical studies using tumor xenografts, pediatric brain tumors were 11-fold more sensitive to G207, compared with glioblastomas in adults.
The researchers hypothesized that intratumoral G207 would increase the amount of tumor-infiltrating lymphocytes and thereby convert immunologically “cold” pediatric brain tumors to “hot” and “inflamed” tumors.
