Washington Editor

Oxford BioMedica plc is ready to begin a Phase III trial of TroVax in renal-cell carcinoma, which is envisioned as a fairly quick route to registration for a product with broad possibilities.

The study's protocol has been agreed to through the FDA's special protocol assessment. The company, of Oxford, UK, plans to start the study in the second half of the year.

"It was important to get the FDA to buy into what we're doing," Oxford BioMedica CEO Alan Kingsman told BioWorld Today, noting that the company's lead product is "certainly a new approach" in the cancer vaccine space. TroVax, he said, is a nucleic acid-based vaccine, something between gene therapy and DNA vaccines.

And given that the proposal was submitted to the FDA just two months ago, "we were very pleased with the speed" with which it got regulatory approval of the protocol, Kingsman added.

The trial is designed to test whether adding the immunotherapy to first-line standard of care prolongs the survival of patients with locally advanced or metastatic clear cell renal adenocarcinoma.

TroVax, which targets the tumor antigen 5T4, is made of a poxvirus (MVA) gene transfer system that delivers the gene for 5T4 and stimulates a patient's body to produce an anti-5T4 immune response to destroy tumor cells carrying it.

Notably, renal-cell carcinoma is associated with "very high levels" of 5T4, Kingsman said. "We want a label saying that TroVax can be used in advanced renal-cell carcinoma in a first-line setting with any standard of care."

Oxford BioMedica plans to seek orphan drug designation in the U.S. and Europe for that indication.

Labeled TRIST (TroVax Renal Immunotherapy Survival Trial), the study will randomize about 700 patients to receive either the investigational gene therapy plus standard of care, or placebo with standard of care.

The multicenter trial will take place in the U.S. and Europe, with Eastern Europe expected to accrue patients most quickly because the company will provide standard of care there. Standard of care includes interleukin-2, interferon-alpha or Sutent (sunitinib, from Pfizer Inc.), and treatment will be stratified between those three options to ensure a balance between TroVax and placebo.

The primary endpoint will measure survival, and secondary endpoints include progression-free survival, tumor response rates and quality-of-life scores. The study is expected to last through the end of 2008, Kingsman said, with product registration targeted for 2009, absent any "hiccups" along the way. Oxford BioMedica, a 1995 spinout from Oxford University, also is discussing the trial's design with European regulatory authorities to support approval there, as well.

The study's protocol provides for a safety and efficacy monitoring board to assess the drug combinations at various points throughout its duration. But Kingsman does not expect safety matters to arise.

"It seems to be totally safe," he said, explaining that because the 5T4 antigen is largely absent on normal tissue, TroVax's intended immune response should target only the cancer. There has not been a single adverse event in more than 400 injections to date, with minor injection-site reactions the only issues. To date, more than 100 patients have been treated with TroVax in six clinical trials.

In addition to renal-cell carcinoma, the company also is targeting colorectal cancer as a lead indication for the product, and because its target, 5T4, is broadly distributed throughout a range of solid tumors, TroVax could find even wider use. In a Phase IIb trial in which TroVax was partnered with chemotherapy for metastatic colorectal cancer, all patients exhibited a T-cell response, and 70 percent of them were cytotoxic T-cell responses (CD-8). Later this year, the Southwest Oncology Group is planning to begin a study of TroVax in 120 late-stage breast cancer patients.

"All the big [solid tumors] are potential targets," Kingsman said, except melanoma, which does not express large amounts of 5T4. He called the market opportunity for TroVax "absolutely enormous."

That could explain why TroVax has Oxford BioMedica "very busy with partnership discussions right now," Kingsman said. Noting "substantial interest" from a number of suitors, all of which are interested in global rights to all indications, he said the company had three meetings scheduled in a two-week span. Going forward, it's possible that a deal could get done by the end of this year, but given Oxford BioMedica's existing cash position - the firm raised £30.1 million (US$51.7 million) late last year - there is no need to rush.

"It's much more important that we do the right deal," Kingsman said, "rather than a fast deal."

On Friday, the company's stock (LSE:OXB) lost 1.25 pence to close at 29.25 pence.