An adjuvant clinical trial of SCIB1, a DNA vaccine that targets dendritic cells in vivo , in fully resected melanoma patients

SCIB1 is a DNA vaccine encoding a human IgG1 antibody, with T cell epitopes from gp100 and TRP-2 antigens engineered into its CDRs. It targets dendritic cells in vivo via the high affinity Fc receptor. A clinical trial in stage III/IV melanoma patients showed that doses of 2-8 mg could induce T cell responses in 7/9 patients with no associated toxicity. Overall median survival was 24 months. In this study SCIB1 is used as an adjuvant therapy. Methods: 16 patients with fully resected stage III (9) or stage IV (7) melanoma, were immunised with SCIB1 by Intramuscular electroporation at 0, 3, 6, 12 and 24 weeks. Patients tolerating treatment were allowed to continue treatment for up to 5 years. Results: Thirteen patients received 4mg doses of SCIB1 on 5 occasions and one received 4 doses of 4mg followed by one dose of 2mg. One patient only tolerated administration of three 2mg doses of SCIB1. One patient received three 2mg doses and then two 4mg doses. Seven patients received additional doses of SCIB1. One patient received 3 doses prior to withdrawal due to disease progression and one patient received 5 doses. The other six patients remain on continuation: three have received 5 doses and two have received 6 doses of SCIB1. Apart from soreness at the injection site, there have been no significant toxicities. All sixteen patients showed an epitope specific proliferation response ex vivo and an IFN Elispot response in-vitroafter T cell expansion. Eleven patients responded to all 4 epitopes, three patients to 3 epitopes, one patients to 2 epitopes and one patients to 1 epitope. All patients with continued treatment showed strong T cell memory responses. Currently patients have a median survival time from trial entry of 29.5 months and from diagnosis of metastases of 34 months. Progression free survival is 78% and 72% for stage III and IV respectively and overall survival is 100% for both groups. Only 4 patients have relapsed at 4, 14, 18 and 18 months, since the last relapse there have been no further recurrences for 23 months. Conclusions: These results suggest that SCIB1 may confer protection from recurrence of melanoma with little associated toxicity. This vaccine deserves further evaluation as an adjuvant therapy. Clinical trial information: 2009-017355-10.