Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma

This phase II study was performed to determine the induction of a specific T-cell response, the clinical response rate, and toxicity of vaccination wi th different HLA class I-binding peptide epitopes derived from the melanocy te differentiation antigen tyrosinase in patients with stage IV melanoma. T he study population consisted of 16 patients with metastatic disease and tw o patients who were macroscopically free of disease at study entry after re section of recurrent skin lesions. Patients received intradermal injections of 200 mg peptide corresponding to their HLA type on day 3, and 75 or 150 mu g granulocyte-macrophage colony-stimulating factor on days 1 to 4. Vacci nations were repeated at weeks 2, 4, 6, 10, and 14. Monitoring of peptide-s pecific T-cell frequencies in the peripheral blood was performed using an i nterferon gamma ELISPOT assay. Eleven of the 16 patients with metastatic di sease went off the protocol within the first 10 weeks because of tumor prog ression. Of the five patients with metastatic disease who received all six vaccinations, one patient showed a mixed response with regression of some l ung metastases; two patients with progressive disease before vaccination ha d stable disease for 6 and 18+ months; and two patients had progression of their disease. The two patients who had all their metastases resected befor e vaccination did not have relapses for 6 and 12+ months after vaccination. Induction of tyrosinase-reactive T cells was found in these two patients a nd in two others with metastatic disease, including the one who achieved a mixed response and one with stable disease. This study shows limited clinic al and immunologic activity of HLA class I-peptide vaccination in combinati on with granulocyte-macrophage colony-stimulating factor in stage IV melano ma patients.