GVAX Immunotherapy for Prostate Cancer

GVAX immunotherapy for prostate cancer is comprised of whole cells derived from two prostate cancer lines. As with all GVAX® cancer immunotherapies, the cells are modified to secrete GM-CSF, an immune stimulatory cytokine, and irradiated to arrest growth while still allowing the cells to remain metabolically active to secrete GM-CSF. GVAX immunotherapy for prostate cancer is designed to be administered through intradermal injections on an outpatient basis.  

Program Status

On October 16, 2008, Cell Genesys announced its decision to terminate the VITAL-1 Phase 3 clinical trial of GVAX immunotherapy for prostate cancer. VITAL-1 was a Phase 3 clinical trial designed to compare GVAX cancer immunotherapy as a monotherapy to Taxotere chemotherapy plus prednisone in hormone-refractory prostate cancer patients with metastatic disease who were asymptomatic with respect to cancer-related pain. The primary endpoint of the trial was an improvement in survival. In 2007, the VITAL-1 trial completed enrollment with 626 patients. In January 2008, Cell Genesys announced that the IDMC had completed a pre-planned interim efficacy analysis for VITAL-1 and recommended that the study continue, providing no further information to the Company other than the recommendation to continue the trial. On August 27, 2008, the Company announced that it had requested the IDMC to conduct a previously unplanned futility analysis of VITAL-1. Results of this analysis indicated that the trial had less than a 30 percent chance of meeting its predefined primary endpoint of an improvement in survival. Based on these results, the Company terminated the VITAL-1 trial.
 

On August 27, 2008, the Company announced its decision to terminate VITAL-2 as recommended by its IDMC which, in a routine safety review meeting held that week to review both VITAL-1 and VITAL-2, observed an imbalance in deaths between the two treatment arms of the VITAL-2 study. VITAL-2 study was conducted in patients with symptomatic metastatic hormone-refractory prostate cancer and compared the combination of GVAX immunotherapy plus Taxotere to Taxotere plus prednisone as a control. At the time this study was terminated, the IDMC had reviewed 114 deaths, of which 67 occurred in the GVAX immunotherapy plus Taxotere combination treatment arm and 47 in the Taxotere plus prednisone control arm. A total of 408 patients had been enrolled in the study up to that point in time. The Company has since conducted an initial analysis of the incomplete clinical trial data set that was reviewed by the IDMC in August 2008. The analysis has revealed no apparent imbalance in patient baseline characteristics with respect to both demographic and disease prognostic factors. In addition, no significant toxicities in the GVAX immunotherapy plus Taxotere combination therapy arm were observed that could explain the imbalance in deaths and in fact, the vast majority of deaths in both treatment arms were reported as due to progression of prostate cancer. Of note, fewer treatment cycles with Taxotere were administered to patients in the GVAX immunotherapy plus Taxotere arm compared to the control arm, a difference which was statistically significant. 

Next Steps

In view of the termination of both the VITAL-1 and VITAL-2 trials, Cell Genesys has placed further development of GVAX immunotherapy for prostate cancer on hold, pending a review of the program with its collaborator, Takeda Pharmaceutical Co. Ltd.