According to an announcement made by Transgene and Jennerex, Inc. the final data from a randomized dose-ranging Phase 2 clinical trial of JX594/TG6006 in 30 patients from sites in the U.S., Canada and South Korea with advanced liver cancer demonstrated a statistically important benefit in overall survival for patients receiving high doses of JX594/TG6006 compared to those receiving low doses.
Dr. Tony Reid, M.D., Ph.D., professor of medicine, hematology/oncology, director of clinical investigation, and the tumor growth, invasion and metastasis program, Moores UCSD Cancer Center at the University of California, San Diego presented the data during the late-breaking oral session at the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco, California under the abstract (#LB-1) "A Randomized, Controlled Phase 2 Clinical Trial of JX594, a Targeted Multi-Mechanistic Oncolytic Poxvirus, in Patients with Advanced Hepatocellular Carcinoma: Final Data."
The HEP007 final data showed that the mortality risk for patients receiving the high-dose treatment was reduced by almost 60% with a hazard ratio of 0.41 in comparison with those randomized to receive the low control dose that was one-tenth of the high dose strength. The average survival rate for the high dose group was 13.8 months compared with 6.7 months in the low dose group, with p = 0.029 for superiority of the high dose. According to Kaplan-Meier estimates, 66% of patients in the high dose group were alive at the one- year point compared with 23% in the low dose group. Researchers found that patients tolerated well to the JX594/TG6006 therapy, with patients experiencing transient flu-like symptoms that generally disappeared within 24 hours.
In collaboration with with Jennerex's partners, the researchers conducted the global, randomized, placebo-controlled Phase 2b clinical TRAVERSE trial of JX594/TG6006 in patients with hepatocellular carcinoma (HCC) who failed sorafenib (Nexavar®) treatment to assess survival in advanced HCC patients whose illness had either progressed or shown intolerance after being treated with sorafenib, the current standard care.
Dr. Reid, a clinical investigator on the HEP007 clinical trial commented:
"These data showing an improvement in overall survival are very encouraging - particularly when coupled with the favorable tolerability profile of JX594/TG6006 experienced in this and prior clinical trials. Another therapeutic option to treat patients with HCC, the third leading cause of cancer death globally, is urgently needed."
David H. Kirn, M.D., President and Chief Medical Officer of Jennerex added:
"The strength of these data - showing a statistically significant benefit in overall survival - gives us great confidence in the potential of JX594/TG6006 to benefit patients with liver and other types of cancer world-wide. Based on these clinical data, and clinical data we have previously published, we are accelerating the development of JX594/TG6006. Together with our partners, we are initiating a more expansive late-stage TRAVERSE clinical trial of JX594/TG6006 in HCC, and we are moving into Phase 1/2 trials in additional cancer types, including ras mutant and Erbitux-refractory colorectal cancer."
Philippe Archinard, Chairman and CEO of Transgene concluded:
"The clinical data presented by Jennerex at AASLD once again validates our commitment to JX594/TG6006 and demonstrates that the product could really change the treatment paradigm in liver cancer. Should these findings be confirmed in late stage clinical trials, and notably in the TRAVERSE study, then the chances of JX594/TG6006 coming to the market will be very high."
Other Recent Clinical Data for JX594/TG6006 in Liver Cancer include:
In a second Phase II trial patients received sequential treatment with combined intravenous and intratumoral JX594/TG6006 therapy and sorafenib treatment. The interim data of 15 patients showed tumor responses by Choi criteria, a measure of tumor necrosis, in both injected and non-injected tumors in 8 of 11 patients who could be evalued. The interim data included a subgroup of 10 patients who previously failed sorafenib therapy. Researchers noted tumor responses were maintained for up to 15 months following initiation of JX594/TG6006 treatment. They also observed a substantial tumor necrosis following JX594/TG6006 and sorafenib treatment in 6 of 7 evaluable sorafenib resistant patients (86%).
Hepatocellular Carcinoma: A Global Unmet Need:
20,000 people in the U.S., 55,000 Europeans, 40,000 Japanese and 350,000 Chinese people are affected by Hepatocellular Carcinoma each year making it the fifths most common cancer worldwide and the third leading cause of cancer mortality. More than 600,000 new cases are diagnosed each year resulting in over 90% mortality. At the moment, the only approved agent for HCC is sorafenib (Nexavar®), which is linked to moderate efficacy, i.e. a tumor response rate of ~2%, and a side effect profile that results in one fourth to one third of patients to discontinue treatment.
JX594/TG6006: A Multi-Mechanistic Approach To Targeting Cancer:
JX594/TG6006, a proprietary, engineered oncolytic virus developed to selectively target and destroy cancer cells. It is designed to attack cancer in three different strategies; First the lysis of cancer cells through viral replication, followed by shutting down the blood supply to tumors by vascular targeting and destruction and subsequently by stimulating the body's immune response against cancer cells, or so called active immunotherapy. To date, Phase I and Phase II clinical trials in multiple cancer types have demonstrated that JX594/TG6006 administered either directly into the tumors or systemically, stimulates shrinkage of the tumor and/or necrosis. Researchers observed a well tolerance in over 120 patients treated to date. In addition, researchers established objective tumor responses in a variety of cancers, such as kidney, liver, colon, lung cancer and melanoma. The safety profile for JX594/TG6006 is favorable with predictable and generally mild common side effects of flu-like symptoms, which resolve within 24 to 48 hours.
Written by Petra Rattue