West Coast Editor

A week after presenting positive data from an ongoing Phase II trial with CoFactor, its biomodulator to enhance 5-FU in treatment regimens for metastatic colorectal cancer, Adventrx Pharmaceuticals Inc. said the FDA cleared the way to start a Phase III pivotal trial under a special protocol assessment.

Joan Robbins, chief technical officer for San Diego-based Adventrx, said the company aims to start the Phase III trial at the end of this quarter or the start of the third.

"We're planning for [the study to last] three years right now, with two for enrollment and a year of follow-up, though we'd like to try to accelerate that by adding on more sites," she told BioWorld Today.

The company's stock (AMEX:ANX) closed Monday at $2.78, down 7 cents.

CoFactor is the active metabolite of leucovorin, which has been proved to boost 5-FU's (5-fluorouracil) activity, but CoFactor "doesn't require any of the metabolic steps that leucovorin usually needs to assist 5-FU, [which] can't inhibit the DNA-synthesis mechanism without this biomodulator," Robbins said.

In the two-arm study, folate-based CoFactor will be studied as a first-line, combination therapy in patients with metastatic colorectal carcinoma. About 600 patients will be included, half of whom will be treated with CoFactor, 5-FU and Avastin (bevacizumab), from South San Francisco-based Genentech Inc., the highly regarded colorectal cancer drug that recently reported good results against breast cancer, as well. (See BioWorld Today, April 18, 2005.)

The other half of the patients in the CoFactor trial will be treated with leucovorin, 5-FU and Avastin. Progression-free survival is the primary endpoint, defined as the time from start of treatment to time of disease progression or death.

Adventrx also recently got the go-ahead in the UK to start an international Phase IIb trial with CoFactor in metastatic colorectal cancer, and plans to file in the first half of this year for clearance to initiate a Phase III study in pancreatic cancer based in the European Union.

Robbins noted that CoFactor has orphan drug status on both sides of the ocean, "so we get a lot of help in the trial design, and we're [regularly] talking with the agencies to make sure we're following the right path for approval, and we've come up with a plan that seems to be agreeable" to European authorities.

A Phase I/II study in Sweden included five pancreatic cancer patients, three of whom lived almost a year. "It's a small number of patients, but it's a hint of some activity, so we feel it's worth following up on," she said.

At the 96th annual meeting of the American Association for Cancer Research in Anaheim, Calif., about a week ago, Adventrx offered encouraging toxicity and pharmacodynamics data from the ongoing colorectal cancer Phase II trial.

"The good news is, there is no toxicity, which is what we expected, but we needed to demonstrate that," Robbins said. More data from that trial are due later this quarter.

Meanwhile, the Phase III trial to start shortly includes "a lot more patients, but it will be a lot more sites," she said. "With the addition of Avastin, [timely enrollment] becomes a more likely scenario. People are using 5-FU, leucovorin and Avastin in first line in quite a few situations."