Study Published in Science Translational Medicine Reports Favorable Safety and Extended Survival for Brain Cancer Patients Treated with Tocagen’s Cancer-Selective Viral Gene Therapy


Study Published in Science Translational Medicine Reports Favorable Safety and Extended Survival for Brain Cancer Patients Treated with Tocagen’s Cancer-Selective Viral Gene Therapy

SAN DIEGO – June 1, 2016Tocagen Inc., a clinical-stage, cancer-selective gene therapy company, today announced results from a multi-center study of an investigational immunotherapy, Toca 511 & Toca FC, have been published in the June 1, 2016, issue of Science Translational Medicine. The study, conducted in patients with recurrent brain cancer, showed extended survival compared to an external control, complete and partial tumor shrinkage determined by independent radiology review and favorable safety and tolerability profiles. This article marks the first peer-reviewed publication describing the study of a retroviral replicating vector administered to humans. Timothy Cloughesy, M.D., director of the UCLA, Neuro-Oncology Program, is the lead author of the paper.

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

  • In the published study conducted by Tocagen, 43 patients with recurrent HGG treated with Toca 511 & Toca FC had a median overall survival of 13.6 months and a probability of survival at 24 months of 31.6%.
  • In the 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 probability of survival at 24 months were 13.6 months and 29.1%, respectively, compared to 7.1 months and 9.1% for an external control of matched GBM patients who received the standard of care chemotherapy drug lomustine.
  • Importantly, Toca 511 & Toca FC had a favorable safety profile and was well tolerated by patients.

“The safety and survival data described in this manuscript are very promising. Seeing a probability of 40 percent survival at 2 years is extraordinary for patients with recurrent brain cancer and consistent with the proposed immune mechanism for this approach,” said Tom Mikkelsen, M.D., co-director of the Hermelin Brain Tumor Center at Henry Ford Hospital and president and scientific director of the Ontario Brain Institute. “Given the high unmet need and extremely limited treatment options for these patients, we are encouraged by these data and look forward to advancing this potential new treatment option for patients suffering from this devastating disease.”

Survival results from the studies are summarized in the table below.

  Median Overall Survival (Months) Overall Survival Probability at 24 Months
Efficacy evaluable population receiving Toca 511 & Toca FC  
Recurrent HGG patients in all dose cohorts (n=43) 13.6 31.6%
Recurrent HGG patients in higher dose cohorts (n=32) 14.4 40.0%
First or second recurrence GBM patients in all dose cohorts (n=27) 13.6 29.1%
External control population receiving lomustine
Matched first or second recurrence GBM patients                (n= 84) 7.1 9.1%

Tumor samples from patients surviving greater than 12 months after treatment displayed a unique survival-related mRNA expression signature which may help support the observed clinical activity of the treatment. Statistically significant increases in CD4+ T cells in the blood were observed, suggesting immune activation may be involved. Also, durable complete and partial shrinkage of tumors reported by independent radiology review were observed in the higher dose groups. Seven of eight patients with stable disease were also in the higher dose cohorts.

“Brain cancers, including glioblastomas, are sensitive to the anticancer drug 5-FU, but side effects from systemic treatment limit its clinical utility. Tocagen’s approach minimizes side effects by producing 5-FU within the tumor, allowing it to selectively destroy cancer cells and also activate the immune system. In addition, 5-FU kills immunosuppressive cells, further powering the immune system’s ability to kill the tumor,” said Harry Gruber, M.D., chief executive officer of Tocagen. “The first publication of clinical data describing Toca 511 & Toca FC is an important accomplishment for a large number of individuals and groups who have supported this new approach to fighting cancer, including patients and their caregivers, the brain tumor care teams at our clinical sites, the dedicated brain cancer non-profit organizations, the clinical diagnostics team at Siemens Healthcare and our passionate team at Tocagen.”

Dr. Gruber also highlighted these results during a concurrent panel discussion at the Boston CEO Conference.

This study was performed in collaboration with investigators at Cleveland Clinic Foundation, Cleveland, OH; University of California, Los Angeles; University of California San Diego School of Medicine; Henry Ford Hospital, Detroit, MI; Ohio State University, Columbus, OH; Swedish Neurological Institute, WA; and JFK Medical Center, Edison, NJ. MGMT DNA methylation analyses were performed by Ribomed Biotechnologies Inc.

Sites in the United States and Canada are now recruiting patients with recurrent glioblastoma or anaplastic astrocytoma for a Phase 2/3 study of Toca 511 & Toca FC, called Toca 5. Additional sites in Germany, Israel and South Korea are planned. More information about the Toca 5 trial can be found at or by searching using the clinical trial identifier NCT02414165.

“While the pursuit of a potential new treatment option for patients with brain cancer remains our first priority, new preclinical results showing our approach activates the immune system against other tumors has driven our plans to initiate a study later this year for patients with metastatic cancers including colorectal, pancreatic, lung, breast, renal and melanoma,” added Dr. Gruber.

About Toca 511 & Toca FC
Tocagen’s cancer-selective gene therapy platform is built on retroviral replicating vectors (RRVs) 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 RRV, Toca 511, and an investigational drug tablet, Toca FC, designed to be used together. Toca 511 is a conditionally oncolytic virus that delivers selectively to cancer cells a gene which converts Toca FC into 5-FU, a potent anticancer drug, in the tumor microenvironment. 5-FU kills the cancer cells leading to activation of the immune system against those dying cells. 5-FU also kills immunosuppressive myeloid cells, which are a major brake on the immune system in the tumor. Removing this brake dramatically increases the immune activation against the cancer. In summary, Toca 511 has a duel mechanism of action. 5-FU is a trigger to conditional oncolytic activation of the immune system and to remove an important brake on the immune system, in the tumor microenvironment.

About Tocagen
Tocagen is a clinical-stage, cancer-selective gene therapy 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 investigational product candidate, Toca 511 (vocimagene amiretrorepvec) & Toca FC (extended-release 5-fluorocytosine), 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. More information about the clinical trial can be found at In 2016, Tocagen plans to initiate clinical trials of Toca 511 & Toca FC in newly diagnosed HGG and metastatic cancer, including colorectal, pancreatic, lung, breast, renal and melanoma. Tocagen obtained Fast Track designation from the U.S. Food and Drug Administration for Toca 511 & Toca FC as a treatment of recurrent HGG and Orphan drug designation for the treatment of glioblastoma (GBM), a subset of HGG. Tocagen has received grant support from leading brain cancer foundations, including Accelerate Brain Cancer Cure (ABC2), National Brain Tumor Society (NBTS), American Brain Tumor Association (ABTA), Musella Foundation and Voices Against Brain Cancer (VABC). For more information, visit or follow @Tocagen.×83.png

Jessie2016-06-01 08:30:222016-09-14 10:49:08Study Published in Science Translational Medicine Reports Favorable Safety and Extended Survival for Brain Cancer Patients Treated with Tocagen’s Cancer-Selective Viral Gene Therapy