By Mary Welch

Staff Writer

Citing its excellent accrual and lack of safety concerns to date, Titan Pharmaceuticals Inc. expanded its Phase II study of CeaVac in patients with advanced colorectal cancer into a Phase III trial.

"When we designed the Phase II trial, we essentially designed a Phase III trial except for the number of patients," said Louis Bucalo, Titan's president and CEO. "We are still finalizing the expanded study protocol with the FDA, so we can't disclose many details of the study. The Phase II trial is still blinded so we don't have any data but there is no concerns to date regarding any toxicity of the vaccine."

The Phase II study involved about 200 patients in 45 centers in the U.S. and UK with advanced (Stage IV) colorectal cancer. The study is comparing the safety and efficacy of standard treatment, consisting of 5-fluorouracil (5FU) and Leucovorin, to standard therapy plus CeaVac. The primary endpoint is survival, along with time to disease progression, quality of life, safety and immune responses. The study was slated to last about two years, with the average survival of patients with this advanced cancer being about 14 months.

In May 1998, the company reported preliminary results of the first 15 patients in a Phase I/II study with CeaVac in patients with resected colorectal cancer (stages II, III and IV). The preliminary results suggested a clinical effect, with nine of 15 patients continuing without evidence of disease, including four of eight patients with advanced cancer continuing beyond one year without recurrence.

"CeaVac is the first and only cancer vaccine to consistently generate immune responses against CEA [carcinoembryonic antigen]," said Kenneth Foon, director of the Barrett Cancer Center at the University of Cincinnati in Ohio. Foon and Malaya Chatterjee invented CeaVac. "We wanted to develop a vaccine that has a better chance of breaking the immune system tolerance to CEA," Foon said. "The immune system doesn't recognize CEA as foreign so we prepared a mirror image of CEA as an anti-idiotyte antibody to confuse the immune system. We have treated over 50 patients to date and the results have been phenomenal. In nearly 100 percent of the cases we generated active immunity against CEA."

CeaVac is designed to generate immune responses to CEA, which is expressed in a variety of cancers and highly expressed in colorectal cancer, Foon said.

"We've shown that chemotherapy with standard drugs combined with CeaVac does not interfere with the immune response to CeaVac," Foon said. "This Phase III trial combines standard chemotherapy with or without CeaVac in patients with metastatic colorectal cancer."

CeaVac, licensed to South San Francisco-based Titan in 1995, is currently unpartnered. "It is in our business model to consider looking for a partner when our products are in late-stage development," Bucalo said. "We would consider talking with partners. We think that the immune response profile of CeaVac is excellent and feel we are making good progress in our CeaVac development program."

Titan's stock (AMEX:TTP) closed Monday at $18.375, up 87.5 cents.