Phase II trials of prostate Ca vaccine promising

May 1, 2005

Orlando, FL--A genetically modified vaccine has demonstrated immunogenicity and clinical activity in hormone-refractory prostate cancer patients with metastatic disease, researchers reported in a poster presentation at the 2005 Multidisciplinary Prostate Cancer Symposium.

Orlando, FL-A genetically modified vaccine has demonstrated immunogenicity and clinical activity in hormone-refractory prostate cancer patients with metastatic disease, researchers reported in a poster presentation at the 2005 Multidisciplinary Prostate Cancer Symposium.

The GVAX vaccine for prostate cancer is a whole cell tumor vaccine, produced from two allogeneic prostate cancer cell lines that have not been taken directly from patients. It was genetically modified to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), a natural hormone that is considered by many immunotherapists as probably the best cytokine or agent to turn on the immune system.

"The GM-CSF is supposed to help turn on the individual patient's immune system to recognize those tumor cell antigens and make T-cells and B-cells targeted against the patient's prostate cancer," explained Natalie Sacks, MD, a medical oncologist at the University of California, San Francisco. "The two cell lines in the vaccine provide a broad range of potential antigens and increase the chance that the immune response will be significant for that patient in that patient's specific tumor."

"The patients had a median survival of 26 months in the single-arm phase II trial. This may reflect patient selection bias, but nonetheless, 26 months was a lot longer than we expected, compared to the natural history of the disease," said Dr. Sacks, who is also director for clinical research at Cell Genesys, the maker of the GVAX vaccine for prostate cancer.

Building on the results of the phase II trials, a phase III trial is now underway in hormone-refractory prostate cancer patients with metastatic disease. That trial compares the vaccine to docetaxel (Taxotere) chemotherapy, which has been recently established as the appropriate form of chemotherapy for this patient population. A second phase III trial that will be initiated later this year will also be for metastatic hormone-refractory prostate cancer patients who, unlike those in the current trial, have cancer-related pain.

Phase III trial warranted Michael Carducci, MD, associate professor in oncology and urology at Johns Hopkins University, told Urology Times that he agreed with the decision to take the vaccine into a phase III study, based on the current results.

"I think that the dose response and immunologic activity warrants the large phase III studies that are planned," he said.

Dr. Carducci said he was not aware of any adverse effect of the agent. Its safety profile, PSA response, and immunologic effect suggest that the GVAX vaccine might provide an opportunity to prolong survival in this patient population.

Dr. Sacks described the phase III study as a frontline trial. Six hundred patients will be enrolled, with 300 patients receiving the vaccine and 300 receiving chemotherapy.