Intra-lymph node prime-boost vaccination against Melan A and tyrosinase for the treatment of metastatic melanoma: results of a phase 1 clinical trial.

PURPOSE

The goal of this study was to test the safety and activity of a therapeutic vaccine, MKC1106-MT, in patients with metastatic melanoma.

EXPERIMENTAL DESIGN

MKC1106-MT comprises a plasmid (pMEL-TYR) and two peptides (E-MEL and E-TYR), corresponding to Melan A and tyrosinase, administered by intra-lymph node injection in a prime-boost sequence. All 18 patients were HLA-A*0201 positive and received a fixed priming dose of plasmid and a low or a high peptide dose. Enumeration of antigen-specific T cells was done prior to and throughout the treatment. Patients who did not exhibit disease progression remained on study and could receive up to eight cycles of treatment.

RESULTS

The MKC1106-MT regimen was well tolerated and resulted in an overall immune response rate of 50%. The treatment showed disease control, defined as stable disease that lasted for 8 weeks or more in 6 of 18 (33%) of the patients: 14% and 46% in the low and high peptide dose, respectively. Interestingly, four patients, all with tumor burden largely confined to lymph nodes and Melan A-specific T cells at baseline, showed durable disease control associated with radiologic evidence of tumor regression. There was no noticeable correlation between the expansion of antigen-specific T cells in blood and the clinical outcome; yet, there was evidence of active tumor-infiltrating lymphocytes (TIL) in two regressing lesions.

CONCLUSIONS

MKC1106-MT showed immunogenicity and evidence of disease control in a defined patient population. These findings support further development of this investigational agent and the concept of therapeutic vaccination in metastatic melanoma.