San Francisco based Jennerex, Inc., a private clinical-stage biotherapeutics company and Transgene , a member of the Institut Merieux Group initiated the enrollment and treatment of patients in a Phase 1b clinical trial to evaluate JX-594 (Vaccinia GM-CSF/thymidine kinase-deactivated virus administered by IV infusion) in patients with advanced metastatic, refractory colorectal cancer (CRC). The study will be performed in Korea, where Green Cross Corporation holds market rights for JX-594.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and according to the World Health Organization (WHO), 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.

JX-594 is a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells. JX-594 is designed to attack cancer through three diverse mechanisms of action: 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. Phase I and Phase II clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients. Objective tumor response has been demonstrated in a variety of cancers including liver, colon, kidney, lung and melanoma. Transgene holds an exclusive license to develop and commercialize JX-594 in Europe and neighboring countries.

Green Cross Corporation, a leading company in the development, manufacturing, and commercialization of viral vaccines and other biological products, holds an exclusive license to develop and commercialize JX-594 in South Korea, and Lee’s Pharmaceutical Ltd. holds an exclusive license to develop and commercialize JX-594 in China. “The initiation of this study marks an important step forward in the development of JX-594 for a second major oncology indication. With a significant and growing population of colorectal cancer patients who have failed existing therapies or for whom existing therapies are not appropriate, we believe JX-594, with its unique mechanisms of action and demonstrated tumor response in preclinical models of CRC, may provide an important new therapeutic modality for patients around the world suffering from this devastating cancer,” said David H. Kirn, M.D., president and chief executive officer of Jennerex.

“The study design for this trial builds on our joint experience and positive clinical results using JX-594 to treat liver cancer and represents an important milestone which is our ability to administer multiple doses intravenously,” added Philippe Archinard, chairman and chief executive officer of Transgene.

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The intravenous, open-label, multi-dose-escalation study is being conducted at Samsung Cancer Center in Seoul, South Korea. The study will enroll up to 15 patients with metastatic colorectal cancer that have failed both oxaliplatin-based and irinotecan-based chemotherapy regimens, and whose tumors harbor ras mutations and/ or are refractory to Erbitux therapy. Patients enrolled in the trial will receive biweekly intravenous infusions of JX-594 at one of three dose levels to evaluate the safety, tolerability and maximum tolerated dose of JX-594 for the treatment of CRC.

Promissing results in Liver Cancer
Earlier this year, interim data from a pilot trial using JX-594 followed by sorafenib (Nexavar?) to treat liver cancer patients showed positive results. The data were presented today at the Fourth Annual International Liver Cancer Association Conference in Montreal, Canada. “While these data represent a small number of patients, we are encouraged by the results, particularly with regard to the promising survival data when compared to historical controls and the fact that all patients to date have exhibited disease control with the treatment regimen of JX-594 followed by sorafenib, including patients whose tumors were previously resistant to sorafenib,” Kim said “We expect to report full results from this pilot trial next year and will evaluate the possibility of a larger, randomized clinical trial utilizing this treatment regimen at that time.”

The pilot trial has enrolled a total of nine patients to date, a subset of which has failed previous treatment with sorafenib; seven of the nine patients have been evaluated for efficacy. All patients were treated with a combination of intravenous and intratumoral doses of JX-594 followed by sorafenib. Six out of the seven evaluable patients achieved Choi (necrotic) responses, five out of seven evaluable patients exhibited stable disease as defined by Response Evaluation Criteria in Solid Tumor (RECIST) criteria, and one achieved a partial response by RECIST criteria. In all patients, the treatment regimen was well-tolerated, and sorafenib toxicities were consistent with the documented historical profile. Safety is the primary endpoint of the trial, with a secondary endpoint of disease control rate determined as a response by Choi criteria and/or a response or stable disease by RECIST criteria.

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