Therion Biologics Corp. is moving its lead vaccine candidate into Phase III work.

The Cambridge, Mass.-based company plans to begin this summer a trial evaluating Panvac-VF in metastatic pancreatic cancer patients who have failed treatment with gemcitabine. The FDA signed off on the study, which will be conducted under the agency's special protocol assessment (SPA) program. It ensures that if the trial successfully meets its primary endpoint - in this case, overall survival compared with best supportive care or palliative chemotherapy - the data will provide the basis for an efficacy claim in an eventual new drug application.

"Therion has treated over 700 patients with its vaccines, but up until two years ago in May 2002 had never filed its own IND," Therion President and CEO Mark Leuchtenberger said. "This hopefully accelerates us into the front ranks of people trying new active immunotherapy approaches. There are just a few of us in pivotal trials looking for results inside a two-year time frame."

The controlled trial will enroll 250 advanced pancreatic cancer patients who will be randomized 1-to-1 to receive either Panvac-VF or a control treatment. The privately held company expects 50 to 60 U.S. sites to be involved, and the study's recruitment and treatment will last until the end of next year.

Those in the treatment arm will receive an initial priming dose of Panvac-VF plus granulocyte macrophage-colony stimulating factor to initiate a cancer immune response, followed by a series of booster vaccinations to sustain the response. Control treatment will consist of either best supportive care or palliative chemotherapy such as capcitabine, irinotecan or 5-fluorouracil.

Secondary endpoints include safety, quality-of-life parameters, change in serum tumor antigen levels, response rate and disease stabilization.

"This is a second-line indication where there is neither an approved therapy, nor even a consistent standard of care," Tom Schuetz, Therion's chief medical officer, said. "The primary endpoint is overall survival, and the standard statistical assumptions went into the powered calculations."

He noted that about 30,500 patients are diagnosed with pancreatic cancer in the U.S. every year, with mortality numbers of about 29,700. Their mean overall survival is about six months at diagnosis, although for patients who fail gemcitabine, that time is cut in half. Gemcitabine is the only therapy approved for such patients, though other chemotherapies are used off label.

Panvac-VF is designed to stimulate the immune system to target and destroy cancer cells expressing two proteins - carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) - found on more than 90 percent of pancreatic tumor cells. The vaccine also incorporates Tricom, Therion's triad of co-stimulatory molecules (B7.1, ICAM-1 and LFA-3), to enhance and sustain a targeted immune response against tumor cells.

Therion said the SPA, which comes less than a year after it filed an investigational new drug application for the product, is based on two recent Phase I trials in metastatic pancreatic cancer patients, as well as other clinical studies with the vaccine's components. The latter studies, sponsored by the National Cancer Institute, involved more than 200 patients with various tumor types who were treated with predecessor vaccines.

Results of the two Phase I studies will be released at next month's American Society of Clinical Oncology meeting in New Orleans. They included a total of 22 patients, with one trial evaluating a vaccine with CEA only and the other studying a vaccine with MUC-1 only. Leuchtenberger labeled Panvac-VF a sixth-generation product candidate.

"It's that history of successful experiments that have accelerated this program from an IND phase to a Phase III designation in less than a year," he added. "And we think that the data from the two Phase Is were compelling enough to convince the FDA to grant us Phase III designation."

Leuchtenberger said Therion, which owns all rights to Panvac-VF, plans to steer the product through the Phase III study before evaluating potential partnership opportunities.

In addition to pancreatic cancer, Therion vaccines targeting CEA and MUC-1 have been tested in patients with other tumors that are known to overexpress the two antigens, including breast, lung and colorectal cancers. Therion and the National Cancer Institute in Bethesda, Md., are planning up to 18 additional trials with Panvac-VF in such indications. A few will start this year, with a colorectal cancer trial scheduled to begin within a month, followed by the others in the next couple of years.

Beyond Panvac-VF, the company said it is pursuing a similar development approach with its second vaccine candidate, Prostvac-VF, which is in a Phase II trial for prostate cancer. Both use the same technology platform, priming with a vaccinia pox and boosting with a fowl pox, as well as the same Tricom set of co-stimulatory molecules. But Prostvac-VF uses the gene for prostate-specific antigen inside its vectors.

The double-blinded trial is recruiting 120 men with metastatic prostate cancer who are hormone refractory, Schuetz said, and randomizing them in a 2-to-1 ratio to receive Prostvac-VF or an empty viral vector control. Its primary endpoint is progression-free survival at 24 weeks, as measured by an increase in the number of bone or lymph node metastases. With enrollment about a third accrued, he said the company expects to have results next year.

A vaccine for colon cancer is being developed through a partnership with Aventis Pasteur Ltd., the vaccines business of Aventis SA, of Strasbourg, France. The product, which targets CEA, is in a Phase II trial under the direction of Aventis Pasteur.