Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma.

The effectivenes of cancer vaccines in inducing CD8(+) T-cell responses remains a challenge, resulting in a need for testing more potent adjuvants. Our objective was to determine the safety and immunogenicity of vaccination against melanoma-related antigens employing MART-1, gp100, and tysosinase paptides combined with the TLR9 agonist PF-3512676 and local granulocyte macrophage-colony stimulating factor in oil emulsion. Using continuous monitoring of safety and a 2-stage design for immunologic efficacy, 20 immune response evaluable patients were targetted. Vaccinations were given subcutaneously on days 1 and 15 per cycle (1cycle=28 d) for up to 13 cycles. Interferon-γ enzyme-linked immunosorbent spot was used as the primary assay measuring the frequency of peripheral antigen-specific CD8(+) T cells at days 50 and 90 compared with baseline (target ≥ 9/20 immunologic responses). Clinical responses were measured by Response Evaluation Criteria In Solid Tumors every 8 weeks. Twenty-two (including 20 immune response evaluable) melanoma patients were enrolled. All had American Joint Committe on Cancer stage IV (5M1a, 6M1b, 11M1c) and most had previously received therapy. Eight had previously treated brain metastases. An average of 3.5 cycles of vaccination per patient was administered. Clinical response data were available for 21 patients. There were 2 partial response and 8 stable disease lasting 2-7 months. One patient with ongoing partial response continued on treatment. At a median follow-up of 7.39 months (range, 3.22-20.47 mo), median progression-free survival was 1.9 months (90% confidence interval, 1.84-3.68) and median overall survival was 13.4 months (90% confidence interval,11.3-∞). No regimen-related grade 3/4/5 toxicities were observed. There were 9/20 patients with positive enzyme-linked immunosorbent spot at day 50 and/or day 90. Our adjuvant regimen combining PF-3512676 and granulocyte macrophage-colony stimulating factor was safe and is worthy of further testing with these or alternative peptides, potentially in combination with antibodies that target immunoregulatory checkpoints.