IMCT-20ASSOCIATION OF SURVIVAL AND PROGRESSION-FREE SURVIVAL WITH IMMUNE RESPONSE IN HLA-A2+ NEWLY-DIAGNOSED GBM PATIENTS IN RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 TRIAL OF DENDRITIC CELL (DC) IMMUNOTHERAPY WITH ICT-107

BACKGROUND: Clinical outcomes were associated with immune response of HLA-A2+ patients enrolled in a randomized phase 2 trial of ICT-107. METHODS: 124 patients (77 HLA-A2+), randomized 2:1, received ICT-107 (autologous DCs incubated with 6 synthetic peptide CTL epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL-13Rα2) or matching control (un-incubated DC). Immune response was determined by a functional ELISPOT assay pre- and post-treatment (ICT-107 30.5% vs. 15.5% in controls). Determination of p-values and significance between dependent variables and overall survival (OS) or progression-free survival (PFS) was performed using log-rank test. Fisheru0027s exact tests were performed for association between extended overall survival (EOS: OS u003e 22.2 months) and extended progression-free survival (EPFS: PFS u003e 16.5 months) and the same variables. RESULTS: HLA-A2+ patients showed evidence of immune response being associated with both OS and PFS. After determining HLA-A2 ELISPOT responders (responders) using a comprehensive scoring system, responders had a median OS of 23.1 months versus 13.7 for non-responders (p = 0.0673). Similarly, responders had an EOS percentage of 52% versus 29% non-responders (p = 0.0615). Further, responders had a significantly higher percentage of EPFS (41% versus 15%, p = 0.0259). When censored to 7.5 months post-treatment, immune response was found to significantly improve OS (median 17.6 months versus 13.7, p = 0.0018). Level of IL-12 production can be linked to survival. High IL-12 producers had a median OS of 20.6 compared to 15.4 for low producers (p = 0.0515). Within the treatment group, the difference was larger, with medians of 23.3 months versus 15.2 (p = 0.0654), and high producers had a significantly higher percentage of EOS (54% versus 31%, p = 0.0426) and EPFS (43% versus 19%, p = 0.0293). CONCLUSIONS: The associations identified between clinical outcomes of OS and PFS with immunologic response provide support for the efficacy of ICT-107 in HLA-A2+ patients due to a biologic T cell response.