TG4023 is being developed to treat primary tumors of the liver (HCC) and metastatic colorectal cancer (mCRC).
Transgene’s TG4023 is a gene-directed enzyme pro-drug therapeutic candidate for the treatment of solid tumors accessible to intra-tumoral injection. The product candidate is based on the MVA virus carrying a highly potent suicide gene, FCU1, derived from the Saccharomyces cerevisiae cytosine deaminase and uracil phosphoribosyltransferase. FCU1 encodes a bifunctional chimeric protein that efficiently converts the noncytotoxic compound 5-fluorocytosine (5-FC) into 5-fluorouracile (5-FU) and 5-FUMP lethal metabolites. The anti-metabolite 5-FU has been used for more than 40 years in the treatment of cancers from various origins, such as digestive tract, ovary, or breast. Passive diffusion of the 5-FU ensures an impressive bystander effect with the ability to kill 100 per cent of a tumor cell population comprising only 1 per cent FCU1-transduced cells. Moreover, by having the tumor cell itself manufacture the lethal cancer drug which acts locally this approach abrogates the 5-FU systemic toxicity.
Worldwide, colorectal cancer strikes approximately 950,000 people each year and accounts for over 500,000 annual deaths. Up to 70 per cent of patients with colorectal cancer eventually develop liver metastasis (mCRC). In 30 to 40 per cent of these patients, metastasis are still confined to the liver at the time of diagnosis. Of these patients only 20 per cent are candidates for surgery due to size, distribution and/or accessibility of the tumor(s), leaving the majority of the population only with the choice of palliative treatments (about 130 000 patients per year in the US and EU).
Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, accounting for about 500,000 deaths per year. Both in Asia and in the Western world, most HCC tumors occur in patients with cirrhosis of the liver (60-80 per cent of diagnosed HCC). Chronic infection with the hepatitis B virus and hepatitis C virus also increases the risk of developing HCC. Although early detection of the tumors results in increased resectability rate (able to be removed by surgery), the number of patients with HCC that are amenable for surgery remains rather low. Of the 564,000 worldwide new cases each year, 65 per cent of patients are considered not eligible for surgery or liver transplantation. For these 360,000 patients, only palliative local treatments such as percutaneous ethanol injection, radiofrequency ablation and transcatheter arterial chemoembolization are available and with poor results.
Transgene announced, on the 4th November 2009, the enrolment the first patient in the phase I clinical trial of TG4023. The phase I trial will take place in 6 centres in France and should enrol some 20 patients with primary or secondary hepatic tumors mainly related to metastatic colorectal cancer (mCRC) or hepatocellular carcinoma (HCC). The trials primary endpoint is safety and determination of the maximum tolerated dose (MTD) of TG4023.
TG4023 has also shown promising preclinical results in different tumor models: head and neck, breast cancers and glioblastoma.
Related press releases :
| November 4, 2009 |
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Transgene: First Patient enrolled in Phase I Trial of TG4023 for the Treatment of Liver Tumours |