Phase I study in metastatic melanoma patients showed early evidence of antitumor activity.

Scientists at Jennerex and their academic collaborators published data from a Phase I dose-escalating study evaluating intravenous administration of the vaccinia-vaccine-derived oncolytic virus JX-594 in 23 patients with metastatic solid tumors. The study data, described in Nature, showed that JX-594 selectively infected, replicated, and expressed transgene products in cancer tissue after intravenous infusion, in a dose-related fashion and without affecting normal tissues. The team claims the positive trial results represent the first time that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans.

In their paper titled “Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans,” Jennerex’ David H. Kirn, Ph.D., and colleagues say dose-related antitumor activity was also demonstrated, and it correlated with delivery and replication of JX-594. New tumor outgrowth following treatment with JX-594 was in addition less frequent in patients treated with high doses than with low doses, indicating suppression of microscopic tumor foci: six of eight patients in the two highest-dose groups demonstrated tumor shrinkage or stabilization.

“Intravenous delivery is crucial for cancer treatment because it allows us to target tumors throughout the body as opposed to just those that we can directly inject,” comments senior co-author John Bell, M.D., a senior scientist at the Ottawa Hospital Research Institute, which has collaborated with Jennerex on development of JX-594. Dr. Bell also co-founded Jennerex with David Kirn. “These results are promising, especially for such an early-stage trial, with only one dose of therapy,” Dr. Bell continues. Additional studies are now in the works.

JX-594 is engineered for viral thymidine kinase gene inactivation, and expression of transgenes encoding human granulocyte-macrophage colony stimulating factor (GM-CSF) and b-galactosidase (b-gal). The candidate is designed to trigger cancer cell lysis (through viral replication), reduce tumor blood supply through vascular targeting and destruction, and stimulate the body’s own immune response against cancer cells.

French firm Transgene holds an exclusive license to develop and commercialize JX-594 in Europe and neighboring countries. Green Cross retains an exclusive license to develop and commercialize JX-594 in South Korea, and Lee’s Pharmaceutical holds an exclusive license to develop and commercialize JX-594 in China.

Intravenous JX-594 is separately being evaluated in an open label dose-escalation study in colorectal cancer patients who have failed existing therapies and are refractory to or unsuitable for Erbitux therapy. The Korean study, initiated in December 2010, will evaluate biweekly intravenous infusions of JX-594 at one of three dose levels to determine safety, tolerability, and maximum tolerated dose.

Intratumorally administered JX-594 has been evaluated in Phase I and II trials for treating a range of cancers including hepatocellular carcinoma (HCC) and metastatic melanoma. Positive data from a proof-of-concept study evaluating JX-594 in metastatic melanoma patients was published in Molecular Therapy in August. Positive preliminary data from a randomized dose-ranging Phase II trial testing intratumoral JX-594 in patients with advanced liver cancer were reported in May and showed early evidence of survival benefit among patients treated with the highest dose of JX-594. A placebo-controlled Phase IIb clinical trial with JX-594 in patients with HCC patients who have failed sorafenib (Nexavar®) treatment is planned to start during 2011. This global trial, conducted by Jennerex and its partners, will evaluate patient survival following JX-594 therapy.

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