GVAX Immunotherapy for Pancreatic Cancer
GVAX immunotherapy for pancreatic cancer is a non patient-specific investigational product currently being evaluated in investigator-sponsored Phase 2 clinical trials in patients with operable (resectable) and inoperable (unresectable) pancreatic cancer. In patients with resectable cancer, it is being evaluated in combination with surgery and standard adjuvant radiation and chemotherapy. In this setting, the goal of GVAX immunotherapy for pancreatic cancer is to reduce or eliminate the potential for minimal residual disease, which frequently occurs following treatment with the current standard of care.
GVAX immunotherapy for pancreatic cancer is comprised of whole cells derived from two pancreatic cancer lines. Using whole cells from two cell lines provides the opportunity to introduce to the patient a wide array of antigens, which could potentially serve to stimulate a broad immune response. Additionally, 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.
This program is being conducted in collaboration with researchers at the Sidney Kimmel Comprehensive Cancer Center at John Hopkins University.
Encouraging Clinical data
In 2008, researchers presented encouraging data from Phase 2 clinical trials of GVAX immunotherapy for pancreatic cancer in both resectable and unresectable pancreatic cancer. Recently presented data is summarized below.
Resectable Pancreatic Cancer
At the 2008 annual meeting of the America Association for Cancer Research, researchers from Johns Hopkins University presented updated data from the ongoing investigator-sponsored Phase 2 clinical trial of GVAX immunotherapy for pancreatic cancer used in combination with surgery and standard adjuvant radiation and chemotherapy.
The trial enrolled 60 patients with resectable pancreatic cancer, of whom 53 were considered high-risk for recurrent cancer based on the finding that their cancer had spread to regional lymph nodes. Following extensive surgical resection of their tumors, patients were administered intradermal injections of GVAX immunotherapy for pancreatic cancer both before and after standard post-operative adjuvant radiation therapy and 5-flourouracil chemotherapy. The first injection of GVAX immunotherapy for pancreatic cancer was given prior to adjuvant chemoradiotherapy and then three additional injections were given following adjuvant therapy at one-month intervals and one final 'booster' injection was given six months later. Patients were monitored for evidence of relapse and survival, as well as the occurrence of adverse events and induction of immune response. The median overall survival observed was 24.8 months. Administration of GVAX immunotherapy for pancreatic cancer was generally well tolerated. The most common side effects were local injection site reactions and flu-like symptoms.
These results compare favorably with published, historical data from multiple single-arm and randomized studies in patients undergoing pancreatic cancer surgery and adjuvant therapy. Median survival for these patients has been reported to be in the range of 17 months to 22 months, including the most recently reported results for gemcitabine chemotherapy.
Unresectable Pancreatic Cancer
In March 2008, the results of a Phase 2 trial of GVAX immunotherapy for pancreatic cancer administered alone or in combination with immune modulatory doses of cyclophosphamide were reported in Clinical Cancer Research (Dr. Laheru et al.) This study, which was sponsored by Cell Genesys, enrolled patients with advanced, unresectable pancreatic cancer. Thirty patients received GVAX immunotherapy alone and 20 patients received GVAX immunotherapy in combination with cyclophosphamide. Median survivals were 2.3 and 4.3 months in the two cohorts respectively. Cellular immune responses to mesothelin were identified in nine of 10 patients receiving GVAX immunotherapy in combination with cyclophosphamide versus four of eight patients who received GVAX immunotherapy alone, suggesting a positive immune modulatory effect of cyclophosphamide. Administration of GVAX immunotherapy for pancreatic cancer was generally well tolerated. The most common side effects were local injection site reactions and flu-like symptoms.
Phase 2 Clinical trials under way
Two investigator-sponsored Phase 2 clinical trials of GVAX immunotherapy for pancreatic cancer are currently under way at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University.
- GVAX immunotherapy for pancreatic cancer in combination with chemoradiotherapy in resectable pancreatic cancer
- Enrollment Closed (see www.clinicaltrials.gov, NCT00084383) - GVAX immunotherapy for pancreatic cancer used in combination with Erbitux® and cyclophosphamide
- Open for Enrollment (see www.clinicaltrials.gov, NCT00305760)