Extended Survival Reported in Brain Cancer Patients Treated With Viral Gene Therapy

Retroviral replicating vector targets high-grade gliomas

Positive findings from a study of an investigational immunotherapy, Toca 511 and Toca FC (Tocagen, Inc.), have been published in Science Translational Medicine. The study, conducted in patients with recurrent brain cancer, showed extended survival compared with matched patients who received the standard-of-care chemotherapy drug lomustine. The article marked the first peer-reviewed publication describing the study of a retroviral replicating vector administered to humans.

High-grade gliomas (HGGs) are among the most common and aggressive primary brain cancers. Approximately 160,000 persons worldwide are expected to be diagnosed with HGG in 2016. The two most common forms of HGG are glioblastoma (GBM) and anaplastic astrocytoma. With current standard of care, patients with newly diagnosed GBM have a median survival of approximately 16 months. Median survival after recurrence is typically seven to nine months.

In the new study, 43 patients with recurrent HGG treated with Toca 511 and Toca FC had a median overall survival of 13.6 months and a probability of survival at 24 months of 29%. In a subset of 27 patients with recurrent HGG in the higher-dose cohorts, median overall survival was 14.4 months, with a probability of survival at 24 months of 40%.

In the subset of 27 patients with recurrent GBM at first or second recurrence, median overall survival and the probability of survival at 24 months were 13.6 months and 29%, respectively, compared with 7.1 months and 9% for the external control group.

Tumor samples from patients surviving longer than 12 months after treatment showed a survival-related mRNA expression signature. Statistically significant increases in CD4+ T cells in the blood were also observed, suggesting that immune activation may be involved in the clinical activity of Toca 511 and Toca FC. In addition, durable complete and partial shrinkage of tumors was observed in the higher-dose groups. Seven of eight patients with stable disease were also in the higher-dose cohorts.

Source: Tocagen; June 1, 2016.