The first patient has been treated in a Phase IIa clinical trial of JX-594 as a neoadjuvant therapy in patients who are undergoing surgery to treat colorectal cancer that has spread to the liver.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and according to the World Health Organization, it accounts for approximately 639,000 deaths worldwide each year. Approximately one in 20 people in the United States will develop CRC during their lifetime, with the risk increasing with age. Ninety percent of all CRC cases are diagnosed in people over the age of 50. The exact cause of colorectal cancer is not known, although there are certain known risk factors that increase the chance of developing colorectal cancer. These risk factors include inflammatory bowel disease, family history of CRC, certain genetic syndromes, smoking, low fruit and vegetable intake and a sedentary lifestyle.

The phase IIa study of JX-594 is being led by Rebecca Auer, MD, surgical oncologist at The Ottawa Hospital, associate scientist at the Ottawa Hospital Research Instituteand assistant professor of surgery at the University of Ottawa in Ottawa, Canada. The clinical trial is being supported by funding from the Ontario Institute for Cancer Research?.

Investigational drug
JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. The investigational drug attacks cancer through three diverse mechanisms of action, including the lysis of cancer cells through viral replication, the reduction of the blood supply to tumors through vascular targeting and destruction, and the stimulation of the body’s immune response against cancer cells.

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An oncolytic virus
JX-594, a Wyeth vaccinia virus with a disruption of the viral thymidine kinase (tk) gene and expression of the immunostimulatory cytokine, granulocyte macrophage colony-stimulating factor (GM-CSF), exploits a specific genetic feature in cancer cells to become activated and lyse the cells, including the EGFR-ras signaling pathway, the cell cycle activation and the loss of cellular interferon defenses.

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Advanced hepatocellular carcinoma
“This trial will allow us to evaluate the use of JX-594 in patients with surgically resectable disease, potentially expanding the role of this therapy in the treatment continuum,” said David H. Kirn, M.D., president and chief medical officer of Jennerex. “We continue to believe that JX-594 could play an integral role in the treatment of cancers and look forward to the results of this trial along with data from the larger Phase IIb study, called TRAVERSE, that is under way in patients with advanced hepatocellular carcinoma.”

“In addition, this study will allow us to expand our analysis of the multi-mechanistic therapeutic activity of JX-594 through the examination of tumor specimens collected during surgery following JX-594 administration,” said John C. Bell, Ph.D., senior scientist, cancer therapeutics, Ottawa Hospital Research Institute, and professor of medicine, University of Ottawa. Dr. Bell is also the program leader of the Ontario Institute for Cancer Research’s Immuno- and Bio-therapies Program.

Progression-free survival and overall survival
This Phase IIa clinical trial will enroll approximately 20 patients with colorectal cancer metastases to the liver. Patients will receive a single injection of JX-594 intravenously or intratumorally two weeks prior to surgical resection. Tumors will be evaluated for evidence of JX-594 replication and pathologic response. Patients will subsequently be followed for progression-free survival and overall survival.

For more information:
Clinical trials:
– Colorectal Cancer: A Phase 1b Dose Escalation Study of JX-594 Administered Every Two Weeks Intravenous Infusion in Patients With Metastatic, Refractory Colorectal CarcinomaNCT01380600
– Liver Cancer: A Phase 2b randomized Single-Blinded Trial of JX-594 Plus Best Supportive Care Versus Placebo Plus Best supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib treatmentNCT01387555
– A Phase 2 Open-Label Pilot Safety Study of JX-594 Administered by IV Infusion Followed by Intertumoral Injection Prior to Standard Soranfenib Treatment in Patients With Unresectable Primary Hepatocellular CarcinomaNCT01171651
– Pediatric: A Phase 1Open-Label, Dose Escalation Study of JX-594 Administered by Intertumoral Injection in Patients With Unresectable Refractory Solid TumorsNCT01169584

Also read:
Phase II Clinical Data for JX-594 Shows Promising Survival Benefit in Advanced Liver Cancer
Clinical Trial to Evaluate Intravenous JX-594 in Patients With Refractory Metastatic Colorectal Cancer Starts in Korea

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