Vion Pharmaceuticals Inc announced the initiation of a Phase I trial of Tapet-CD, its first armed vector, for patients with an advanced or metastatic solid tumor that is no longer considered responsive to available commercial treatments.

In the study, Tapet-CD will be injected directly into a solid tumor on or near the surface of the body. Each patient will also be given 5-fluorocytosine (5-FC) to take orally. The main objective of the study is to determine the maximum safe doses of Tapet-CD and 5-FC. In addition, injected tumors will be examined for extent of Tapet-CD colonization, conversion of the prodrug 5-FC to the active anti-cancer agent 5-fluorouracil (5-FU), and any anti-cancer effects.

Alan Kessman, CEO of Vion, commented, "The initiation of a clinical trial with our first armed vector is an important milestone for the company, and will provide important data to support future studies of intravenously administered Tapet-CD, and also for future studies of other armed Tapet vectors. In addition to its own potential anti-tumor activity, Tapet-CD by direct tumor injection or by intravenous administration may be particularly interesting to combine with radiotherapy, since both the Salmonella bacteria and 5-FU are known to enhance radiotherapy anti-tumor effects."

Tapet-CD is a weakened Salmonella typhimurium bacteria engineered to produce the enzyme cytosine deaminase (CD). The enzyme converts 5-fluorocytosine (5-FC), an agent that is generally well-tolerated and is approved for the treatment of fungal infections, into the standard anticancer agent, 5-fluorouracil (5-FU).

In preclinical models, Tapet-CD bacteria producing the CD enzyme accumulate to much larger numbers in tumors compared to normal tissues. The Tapet-CD bacteria convert 5-FC to 5-FU within the tumor tissue, resulting in high levels of 5-FU only within the tumor, and producing antitumor effects superior to the Tapet bacteria alone. In these preclinical models, the combined administration of Tapet-CD and 5-FC selectively produce higher levels of 5FU in the tumor than could be delivered by systemic administration of 5FU alone.

Tapet-CD was derived from the parent, unarmed vector VNP20009, which is currently undergoing evaluation in Phase I human clinical trials. A Phase I trial of VNP20009 by direct injection into solid tumors was recently completed, and demonstrated that direct intra-tumoral injections are well-tolerated, produce colonization of the injected tumor for a minimum of two weeks, and can be associated with anti-tumor effects. Phase I trials of VNP20009 by intravenous injection are ongoing to determine the optimal dose and schedule for colonization of tumors throughout the body.