Study Designed to Serve as a Potential Registrational Trial
SAN DIEGO – Dec. 3, 2015 — Tocagen Inc. a clinical-stage, cancer-selective immunotherapy company, today announced that the first patient has been enrolled in the Phase 2 portion of its randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC against current standard of care in patients with first or second recurrence of glioblastoma or anaplastic astrocytoma who are undergoing resection.
“The current lack of effective therapies for high grade gliomas, such as glioblastoma and anaplastic astrocytoma, leaves doctors with few options for treating patients,” said Tom Mikkelsen, M.D., co-director of the Hermelin Brain Tumor Center at Henry Ford Hospital, which enrolled the first patient in the Toca 5 clinical trial. “Tocagen’s cancer-selective immunotherapy has shown encouraging results to date and provides new hope for people with these types of brain cancer.”
The primary endpoint for the Toca 5 clinical trial is overall survival and the study is expected to enroll patients in multiple countries. Investigators may choose chemotherapy (lomustine or temozolomide) or antiangiogenic therapy (bevacizumab) for the control arm. Tim Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program, is the principal investigator in the United States for the Toca 5 clinical trial.
“Enrolling the first patient in the Toca 5 trial is an important step in advancing this potential new treatment option for patients with high grade glioma,” said Harry Gruber, M.D., chief executive officer of Tocagen. “We are especially thankful to our clinical trial sites and the broader brain tumor community for their continued support of Tocagen in our shared fight against brain cancer.”
High grade gliomas (HGGs) are among the most common and aggressive primary brain cancers. The total number of newly diagnosed HGGs expected in 2015 is about 160,000 worldwide and about 14,000 in the United States. The two most common forms of HGGs are glioblastoma (GBM) and anaplastic astrocytoma. Patients with newly diagnosed GBM who receive maximal therapy have a median survival of approximately 16 months. Median survival after recurrence is approximately seven to nine months.
As of Sept. 25, 2015, Tocagen has treated 116 patients with recurrent HGG with Toca 511 & Toca FC in three ongoing Phase 1 clinical trials. In these studies, potential benefits were found, including extended overall survival and a favorable safety profile. In particular, patients with recurrent HGG who received Toca 511 at the time of surgical resection of tumor, which mirrors the delivery method in the Toca 5 trial, had a median survival of 13.6 months (N=43) and a 12 and 24-month survival rate of 52.5 percent and 31.6 percent, respectively. A summary of clinical data from Tocagen’s ongoing Phase 1 clinical trials can be found on Tocagen’s website.
Tocagen’s cancer-selective gene therapy platform is built on retroviral replicating vectors (RRVs) which are designed to selectively integrate into the DNA of cancer cells which then serve as factories for these RRVs to replicate and infect neighboring cancer cells, providing long-term presence of the therapeutic gene(s). Tocagen’s lead product candidate is a combination of an investigational biologic, Toca 511, and an investigational small molecule drug, Toca FC, designed to be used together. Toca 511 is a proprietary injectable RRV that encodes a prodrug activator enzyme, cytosine deaminase (CD). Its selective delivery to cancer cells means that the infected cancer cells selectively carry the CD gene and produce CD protein. Toca FC is an orally administered, proprietary extended-release version of 5-FC, a prodrug that is inactive as an anti-cancer drug. Toca FC is converted into the active anti-cancer drug, 5-FU, at high concentrations in Toca-511-infected cancer cells that are producing CD protein. 5-FU is a well-established anti-cancer agent used effectively in many conventional chemotherapy settings. In addition to the direct killing of Toca 511-infected cancer cells, 5-FU kills neighboring uninfected cancer cells and myeloid derived suppressor cells (MDSCs) in the tumor.
In addition to Henry Ford Hospital, the University of California, Irvine and JFK Medical Center are also recruiting patients. More information about the clinical trial can be found at www.tocagen.com/toca5 or by searching clinicaltrials.gov using the clinical trial identifier NCT02414165.
Tocagen is a clinical-stage, cancer-selective immunotherapy company focused on developing first-in-class, broadly-applicable product candidates designed to activate a patient’s immune system against their own cancer from within. The company is developing its lead product candidate, Toca 511 & Toca FC, initially for the treatment of recurrent high grade glioma (HGG), a disease with significant unmet medical need. Tocagen has initiated the Phase 2 portion of a randomized, controlled Phase 2/3 clinical trial of Toca 511 & Toca FC in patients with recurrent HGG, which is designed to serve as a potential registrational trial. In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in patients with newly diagnosed HGG and other solid tumors. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration, for Toca 511 & Toca FC for the treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. For more information visit www.tocagen.com or follow @Tocagen.