AACR-NCI-EORTC: Gene Therapy Shows Early Efficacy Against Recurrent Brain Cancer

Key Points

  • Within a subgroup of 23 patients that match the entry criteria for an ongoing phase III trial, 5 patients are experiencing a durable complete response with a median of at least 35.7 months.
  • In addition, there were 5 patients who achieved stable disease, bringing the number of patients who derived clinical benefit from Toca 511 to 10 (or 43.4% of the patients who underwent Toca 511 therapy). 

More than a quarter of patients with recurrent high-grade glioma treated with the retroviral vector Toca 511 (vocimagene amiretrorepvec) combined with Toca FC (an extended-release formulation of fluorocytosine, a prodrug of fluorouracil [5-FU]) were alive more than 3 years after treatment, according to data from a subset of patients in a phase I clinical trial presented by Cloughsey et al at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, held October 26–30 in Philadelphia (Abstract A085). The annual symposium is hosted by the American Association for Cancer Research (AACR), National Cancer Institute (NCI), and European Organisation for Research and Treatment of Cancer (EORTC).

“Given the deadly nature of this disease, 3-year survival is rarely reported in the recurrent setting. It is notable that the survival benefit was seen across a range of patients, and not just limited to patients with specific genetic mutations,” said Clark Chen, MD, PhD, Lyle French Chair in Neurosurgery and Head of the University of Minnesota Medical School Department of Neurosurgery in Minneapolis. “This finding indicates that many patients could benefit from this treatment.”

Treatment Details

The treatment for the 56 patients with recurrent high-grade glioma in this clinical trial involved two steps. First, patients were injected with Toca 511, which is a replicating virus that selectively infects actively dividing tumor cells. Once inside the cancer cell, the virus delivers a gene for an enzyme, cytosine deaminase. As the virus replicates and spreads to other cancer cells, it programs them to make CD. Next, patients received a tablet, Toca FC, which is an inert compound. Once inside the cancer cell, cytosine deaminase converts Toca FC into the anticancer drug 5-FU, which kills the cancer cell. In addition to destroying cancer cells, 5-FU kills certain immune suppressive myeloid cells, thus boosting the patient’s immune system to recognize and attack the cancer cells.

“The treatment we tested in this trial delivers local chemotherapy specifically to the brain tumor. Toca 511 and Toca FC work together to turn the brain tumor into a factory that produces an anticancer drug while also activating the immune system through a combination of mechanisms, which together work to attack the cancer,” Dr. Chen said.

More Results

Within a subgroup of 23 patients that match the entry criteria for an ongoing phase III trial (Toca 5), Dr. Chen noted that 5 patients are experiencing a durable complete response with a median of at least 35.7 months. In addition, there were 5 patients who achieved stable disease, bringing the number of patients who derived clinical benefit from Toca 511 to 10 (or 43.4% of the patients who underwent Toca 511 therapy).

“This treatment has a very favorable safety profile,” Dr. Chen added. “The Toca 511 therapy approach spares the body from exposure to systemic chemotherapy while creating high concentration of chemotherapy in the tumor cells and their microenvironment.”

The median survival in this trial is nearly double compared to historical data, according to Dr. Chen. In the subgroup, median survival was 14.4 months compared to approximately 8 months for historical controls. In contrast to the ongoing, durable responses observed in this study, patients treated with the chemotherapy lomustine (Gleostine) had an overall response rate of about 4.3%, which, like bevacizumab (Avastin), was not durable and typically lasted a few months.

A limitation of the study is that it was a single-arm trial without a control group. “The ongoing randomized phase III trial will be important to confirm the promising safety and efficacy results reported in this phase I study,” Dr. Chen noted.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement