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 dose 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 × 106 cells q28d × 6 to 500 × 106 cells prime/300 × 106 cells boost q14d × 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 dose was not established. The median survival time was 35.0 months in the high‐dose 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 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low‐dose group, 13 of 18 (72%) in the mid‐dose group, and 16 of 18 (89%) in the high‐dose 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. Cancer 2008. © 2008 American Cancer Society. This open‐label, multicenter, dose‐escalation study evaluated a GM‐CSF‐secreting, cellular immunotherapy in 80 patients with metastatic hormone‐refractory prostate cancer. Treatment was well tolerated and demonstrated immunogenicity and clinical activity. Phase 3 trials are underway.