US-based clinical stage biopharmaceutical firm Tocagen has dosed the first patient in its clinical trial investigating the intravenous administration of selective cancer therapy Toca 511 & Toca FC, in patients with recurrent high grade glioma (HGG) including glioblastoma multiforme, the most common form of primary brain cancer.

The multicentre, open-label trial is designed to evaluate the safety, tolerability and pharmacokinetics of ascending doses of Toca 511 given intravenously before scheduled tumour removal.

Tocagen said that Toca 511 is also administered into the wall of the resection cavity at the time of tumour removal, followed by cycles of oral Toca FC.

The removed tumour will be tested for the presence of Toca 511, while patients will be monitored for changes in clinical status and clinical response data will be collected.

Henry Ford Hospital vice-chair of department of neurosurgery and principal investigator of the trial Steven Kalkanis said: "Patients diagnosed with recurrent brain cancer have limited treatment options, with patients typically surviving less than eight months, so there is a high level of need for new therapies to fight this disease."

The Henry Ford Hospital neurosurgeon Ian Lee said early data involving intra-tumoral delivery have shown Toca 511 & Toca FC can selectively kill cancer cells and not healthy brain cells.

"As the first centre to enroll a patient in this new study, we look forward to evaluating the potential of this additional delivery approach," Kalkanis said.

Toca 511 & Toca FC is designed to selectively infect and kill cancer cells via a proposed dual mechanism of action.

"We are also advancing our preclinical candidates that are designed to activate the immune system selectively to kill cancer cells."

Firstly, the Toca 511 virus selectively infects and mediates direct cancer cell killing via local production of 5-FU, a potent anticancer agent, and second, the immune system becomes activated selectively against the tumour resulting in long-term, systemic anticancer activity.

Tocagen CEO Harry Gruber said exploring the intravenous delivery of Toca 511 is an important step in the company’s fight against brain cancer and towards expanding the types of cancers it can target using its technology, including metastatic cancers.

"We are also advancing our preclinical candidates that are designed to activate the immune system selectively to kill cancer cells: Toca gamma, which produces gamma interferon within cancer cells, as well as Toca RNAi, which inhibits immune checkpoints in cancer cells," Gruber said.

Currently, the combination of Toca 511 (vocimagene amiretrorepvec) for injection and Toca FC (flucytosine) extended-release tablets, is being evaluated in Phase I/II trials at centres across the US in patients with recurrent high grade glioma, including glioblastoma multiforme (GBM).

An investigational gene therapy, Toca 511 is a retroviral replicating vector (RRV) that is designed to provide a prodrug activator gene called cytosine deaminase (CD) selectively to cancer cells.

Image: Glioma of the left parietal lobe. CT scan with contrast enhancement. Photo: courtesy of Mikhail Kalinin.