CancerVax Corp. is springing back into action as it resumes enrollment in Phase III melanoma studies of its lead product, Canvaxin.
The international trials, designed to study the therapeutic cancer vaccine in patients with Stage III or IV melanoma, were halted nearly a year ago by the company after the FDA raised questions related to Canvaxin's production. At the time the Carlsbad, Calif.-based company said it would work to develop manufacturing-related information, all the while stressing that the hold did not result from any clinical practice or safety concerns.
According to CancerVax, its submission of supplementary information satisfied the agency's concerns.
"It's a cellular-based vaccine, and also is allogeneic, meaning the vaccine is being developed to be given to all patients," CancerVax President and CEO David Hale told BioWorld Today. "The FDA asked us to develop data that would ensure the reproducibility of the cellular product from batch to batch."
Patients already receiving Canvaxin in the Phase III trials continued treatment without interruption. The 1,100-person Stage III melanoma trial has enrolled 639 patients, while the 660-person Stage IV melanoma trial has enrolled 279 patients thus far.
"We think we can complete enrollment in both studies sometime in 2004," Hale said. "I can't tell you exactly when the studies will be completed because they are survival studies. But that point in time should occur sometime in late 2004 or early 2005."
While final data from the Phase III trials remain on the horizon, previously published data shed some light on the product.
Findings published in the Journal of Clinical Oncology indicated that Canvaxin treatment significantly increased overall survival in Stage IV melanoma patients. Of 150 patients who received post-surgical treatment with Canvaxin and 113 who received other or no adjuvant therapy, median overall survival and five-year overall survival were significantly increased for Canvaxin-treated patients (p=0.0001). Results published in the Annals of Surgery showed that Canvaxin treatment also increased overall survival in Stage III melanoma patients. In the retrospective analyses of 2,600 patients, median overall survival and five-year overall survival were significantly higher in Canvaxin-treated patients - 56.4 months vs. 31.9 months and 49 percent vs. 37 percent, respectively (p=0.0001).
The company also received further FDA endorsement in late January when the agency conferred fast-track status on Canvaxin for the metastatic melanoma indication.
"Canvaxin certainly addresses a market with a medical need that hasn't been addressed - late-stage melanoma," Hale said. "This sets certain expectations that we would work with the FDA closer in development of the product and also sets up the potential that there would be an expedited review when we submit our biologics license application."
Canvaxin is composed of three allogeneic tumor cell lines that together express more than 30 tumor- or melanoma-associated antigens. And though its mechanism of action has not been established, CancerVax said research indicates that the antigens expressed in the vaccine stimulate a body's immune system to produce cancer-fighting T cells and antibodies. The company added that Canvaxin's polyvalent nature confers a high probability of an antigenic match with individual patients with melanoma and other solid tumors.
"Now that we have satisfied the partial clinical hold issues, our plan is to work with the FDA on a protocol for evaluating Canvaxin in a large Phase II/III study in late-stage colon cancer," Hale said. "Our hope is that we could begin enrolling patients in that study in the fourth quarter of this year."
Beyond Canvaxin, the company has advanced into preclinical development a pair of angiogenesis inhibitors that are humanized monoclonal antibodies. Another preclinical-stage product being developed by CancerVax is a lung cancer vaccine.