GenVec Inc announced interim Phase I results from the clinical trial of its lead oncology product candidate, TNFerade, in patients with a rare form of cancer known as soft tissue sarcoma. A total of 14 patients will receive the investigational gene-based therapy at leading cancer centers in the United States.

TNFerade delivers the tumor necrosis factor alpha (TNF-alpha) gene using GenVec's proprietary adenovector technology. TNFerade is injected directly into the tumors one or two times per week for up to 6 weeks while the patients are receiving standard radiation therapy. The localized production of the potent anticancer protein, TNF-alpha, is stimulated inside the tumor when the standard radiation therapy is given.

The Phase I study was designed as a dose-escalation safety study testing three doses of TNFerade in patients with soft tissue sarcoma of the extremity. These are generally very large tumors that typically do not respond well to standard therapies. Patients were already scheduled to receive radiation therapy for one of two reasons (a) before surgery to reduce the tumor size or (b) for palliation, to reduce symptoms in patients who cannot undergo surgery to remove the tumor.

TNFerade was well tolerated with no dose-limiting toxicities reported. Maximum tolerated dose was not reached.

Although this study was designed to test the safety of three dose levels of TNFerade in patients with soft tissue sarcoma, evidence of activity on the tumors was also reported. TNFerade treatment plus radiation therapy resulted in an overall objective tumor response rate of 71 per cent(5 out of 7 patients). Objective tumor response rate means that these patients experienced tumor shrinkage between 50 per centand 100 per cent . Two of 7 patients (29 per cent ) experienced a complete response (CR), which is 100 per centtumor eradication. These patients had very large tumors, (3-4 liters), or roughly the size of a watermelon. Three of seven patients (43 per cent ) experienced a partial response (PR), which is tumor shrinkage between 50-99 per cent . One patient had stable disease which means that the tumor size did not change significantly from baseline. One patient had progressive disease, which means their tumor grew more than 25 per cent . Clinicians also noted that CT scans, often used to measure the size of the tumors after treatment, actually underestimated the response rate as compared to the actual tumor response noted on pathological (laboratory) review after surgical removal of the tumor.

Dr. Ralph Weischelbaum, Chairman of the Department of Radiation and Cellular Oncology at the University of Chicago who first reported on the synergistic effects of radiation therapy and TNFerade stated, "The lack of toxicity from this treatment is gratifying and indicates that the approach of local administration of the gene encoding for TNF-alpha, combined with the radiation-inducible switch found in TNFerade, is working in patients with cancer. This is further confirmed by very low blood levels of TNF-alpha, the therapeutic protein is remaining localized, doing its job, and is not getting distributed throughout the body. Furthermore, a 71 per centobjective tumor response rate, including a 29 per centcomplete response rate in patients with very large sarcomas is dramatic and indicates significantly increased activity when TNFerade is added to radiation therapy. This level of activity, combined with the good safety profile suggests a favorable therapeutic window, which should be explored in larger randomized studies."

GenVec plans to present follow-up data on all 14 patients from its dose- escalation safety study of TNFerade in patients with soft tissue sarcoma in the first half of 2003.