BioWorld International Correspondent

LONDON - Oxford BioMedica plc released data from three ongoing Phase II trials of its cancer gene therapy product, TroVax, in metastatic colorectal cancer, showing all 33 patients mounted an immune response, while in the two most advanced trials the tumors in 18 of 19 patients evaluated to date responded to treatment.

"This is right at the top end of anything achieved with a cancer vaccine," Susan Kingsman, senior vice president of research, said in a conference call.

In the first two trials patients received six TroVax injections - two before, two during and two after standard chemotherapy. All those who have reached the interim stage of the trials have shown an immune response to the 5T4 tumor antigen that is expressed by TroVax.

The secondary endpoint - clinical benefit - exceeded expectations, with five patients showing stable disease, 10 having more that 30 percent tumor shrinkage, and three patients having total tumor shrinkage. In the (much larger) pivotal trials that supported approval of the two chemotherapy regimens alone, 41 percent and 50 percent of patients, respectively, showed a clinical response.

The trials have not been running long enough to assess if clinical response translates into survival benefit, but Kingsman said the response rate is encouraging.

In two earlier Phase I/II studies there was a highly significant correlation between immune response rate and time to disease progression. That translated into improved overall survival. One patient with late-stage colorectal cancer from the first trial of TroVax, which began in January 2001, is still alive. First survival data from the Phase II trials are expected by the end of 2005.

In the third Phase II trial, being run by Cancer Research UK, eight patients have received TroVax as an adjunct to surgery to remove liver metastases. While all eight have shown an immune response, the trial is not far enough along to assess clinical benefit.

To date, more than 65 patients with advanced colorectal cancer have been treated with TroVax, which consists of a poxvirus vector that delivers the gene for 5T4. The antigen is found on a wide range of solid tumors, and as its presence is correlated with poor prognosis, it is thought to have a possible mechanistic role in tumor growth. Oxford-based Oxford BioMedica has exclusive rights to both the gene and the antigen.

Kingsman said the company is in partnering discussions and hopes to get marketing approval in 2008-2009. Commercial-scale manufacturing is in place. "The safety profile is so good, we feel it will put us in good standing for discussions with the FDA," she said.