Phase 1 trial
The phase 1 trial included four dose cohorts of children and adolescents with a pathologically proven malignant supratentorial brain tumor of at least 1 cm in diameter that had progressed after surgery, radiotherapy, or chemotherapy.
There were three patients in each dose cohort. One cohort received 107 plaque-forming units, the second received 108 PFU, the third received 107 PFU with 5 Gy of radiation, and the fourth received 108 PFU with 5 Gy radiation.
The patients first underwent stereotactic placement of up to four intratumoral catheters. The next day, they underwent infusion of the assigned PFU doses by controlled-rate infusion over 6 hours.
For the patients who received radiation, 5 Gy were administered to the gross tumor volume within 24 hours following G207 administration.
Among the 12 patients, tumors included 10 glioblastomas, one anaplastic astrocytoma, and one high-grade glioma not otherwise specified.
Responses (radiographic, neuropathologic, or clinical) occurred in 11 of the 12 patients.
Four patients were still alive 18 months after treatment, “which exceeds the life expectancy for newly diagnosed patients,” Dr. Friedman noted. Most patients die within 1 year of being diagnosed with pediatric glioma.
The investigators also found evidence to suggest that survival may be improved for patients who experience seroconversion after exposure to HSV-1 in comparison to patients with HSV-1 antibodies from prior HSV-1 infection. The median overall survival was 18.3 months for patients who experienced seroconversion, compared with 5.1 months for three patients who, at baseline, had IgG antibodies to HSV-1.
No dose-limiting toxicities or serious adverse events attributable to G207 occurred. There were 20 grade 1 adverse events that were potentially related to G207.
There was no evidence of peripheral G207 shedding or viremia, the investigators reported.
Radiation effect?
Commenting on the results in an interview, Dr. Kaufman noted that the sample size (12 patients) in this study was too small to determine whether the radiation received by patients in two of the four cohorts had any additive effect.
“Whether to move forward with virus alone or to add the radiation remains an open question that I don’t think was adequately answered,” he said.
Regarding the evidence suggesting that survival was better among patients who did not have antibodies to HSV-1 at baseline, Dr. Kaufman said, “We’ve looked at that in the melanoma population but haven’t seen any correlation there, so that’s interesting.”
The finding could be related to the fact that this was a pediatric population, or it could be related to the location of the tumors in the brain.
“It’s an interesting finding, and it suggests that, in future studies, they might want to select patients who are HSV seronegative up front,” he said.
Dr. Friedman and colleagues are currently planning a phase 2 trial of G207 with 5 Gy of radiation for children and adolescents with recurrent or progressive high-grade gliomas.
The study was supported by grants from the FDA, the National Institutes of Health, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation, the Department of Defense, the Andrew McDonough B+ Foundation, and the Kaul Pediatric Research Institute; by NIH/National Cancer Institute Cancer Center support grants to the University of Alabama at Birmingham and to the Memorial Sloan Kettering Cancer Center; and by Kelsie’s Crew, Eli’s Block Party Childhood Cancer Foundation, the Eli Jackson Foundation, Jaxon’s FROG Foundation, Battle for a Cure Foundation, and Sandcastle Kids. Dr. Friedman has received grants/support from the organizations listed above, as well as from Eli Lilly and Pfizer. Dr. Kaufman disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
