Phase I trial of ImmunoBody in melanoma patients

ImmunoBody is a DNA vaccine encoding a human IgG1 antibody with T cell epitopes grafted into its CDR regions. SCIB1 has 3 epitopes grafted from gp100 and one from TRP-2 antigens. The vaccine targets dendritic cells in vivo and stimulates high avidity T cells which result in elimination of established tumors in pre-clinical models. A clinical trial was conducted to determine safety and its ability to induce cellular immune responses. Methods: The vaccine was administered via Intramuscular injection with electroporation at 3 weekly intervals for 3 vaccinations, then at 3 and 6 months. In part 1 of the study,one patient with Stage III and 8 with stage IV melanoma were given escalating doses of SCIB1. The 4mg dose was selected for an expansion cohort (part 2) in fully resected patients, 8 with stage III and 6 with stage IV melanoma. Due to lack of toxicity a five further patients with stage IV M1b disease were given 8mg doses. Results: No dose-limiting toxicities were observed. The most common adverse event was injection site pain. 4/6 patients in the 2mg/4mg cohorts who received >3 doses of SCIB1, are still alive with a median survival time of 26 months. One patient had multiple tumor lesions which all decreased in size or disappeared following treatment except for one lesion which was resected. Immunohistochemistry demonstrated strong expression of PD.L1 on the tumor cells. All patients in part 2 remain alive and only three have progressed. The median survival time in Part 2 is 17 months from study entry and 22 months from diagnosis of metastatic disease. In part 1, one patient in the 0.4mg cohort, all three patients in the 2mg dose cohort and two patients in the 4mg dose cohort mounted an immune response to the vaccine-encoded antigens. 4/5 patients in the 8mg cohort made a γIFN elispot response after T cell expansion in-vitro with frequencies exceeding 2% of blood lymphocytes. In part 2, all 14 patients responded immunologically. Six patients responded to all 4 epitopes, five patients responded to 3 epitopes and 3 patients responded to 2 epitopes. Conclusions: We demonstrate that SCIB1 is safe. Of 25 evaluable patients, 23 have shown immune responses following repeat dosing with 2 -8 mg of SCIB1. Detection of an objective clinical response and overall survival times are encouraging. Clinical trial information: NCT01138410.