Vion Begins Phase I Clinical Trial of First Armed TAPET(R) Vector
NEW HAVEN, Conn., Feb 4
Vion Pharmaceuticals, Inc. Vion announced today the initiation of a Phase I trial of TAPET(R)-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(R)-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(R)-CD and 5-FC. In addition, injected tumors will be examined for extent of TAPET(R)-CD colonization, conversion of the prodrug 5-FC to the active anti- cancer agent 5-fluorouracil (5-FU), and any anti-cancer effects. The trial is currently open for patient accrual at the Mary Crowley Research Institute in Dallas, Texas, with additional sites expected to open in the future.
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(R)-CD, and also for future studies of other armed TAPET(R) vectors. In addition to its own potential anti-tumor activity, TAPET(R)-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(R)-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(R)-CD bacteria producing the CD enzyme accumulate to much larger numbers in tumors compared to normal tissues. The TAPET(R)-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(R) bacteria alone. In these preclinical models, the combined administration of TAPET(R)-CD and 5-FC selectively produce higher levels of 5FU in the tumor than could be delivered by systemic administration of 5FU alone. TAPET(R)-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. |
