Phase 1/2 dose-escalation study of a GM-CSF-Secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer

BACKGROUND. This open-label, multicenter, dose-escalation study evaluated multiple (Jose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte macrophage-colony-stimulating factor (GM-CSF). METHODS. Dose levels ranged from 100 X 10(6) cells q28d X 6 to 500 X 10(6) cells prime/300 X 10(6) cells boost q14d X 11. Endpoints included Safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics. RESULTS. Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated (lose was not established. The median survival dine), was 35.0 months in the high-close group, 20.0 months in the mid-dose, group, and 23.1 months in the [low-dose group). PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in I patient. The proportion of patients who generated an antibody response to I or both cell lines increased with close and included 10 of 23 (43%) in the low-close group, 13 of 18 (72%) in the mid-close group, and 16 of 18 (89%) in the high-close group (P =.002; Cochran-Armitage trend test). CONCLUSIONS. This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway.