Biomarkers associated with clinical outcome in advanced non-small cell lung cancer patients treated with TG4010

Abstract

3027 Background: TG4010 is a targeted immunotherapy product. It was tested in combination with first-line chemotherapy in a randomized, controlled, multicenter phase II study in patients with advanced non small cell lung cancer (NSCLC) (ASCO 2008- Abstract No 8023) Methods: In addition to clinical endpoints, immune parameters were tested. Blood samples were drawn prior to therapy (day1) as well as at day 43 (after 6 injections of TG4010). Lymphocyte populations were assessed by 5-color flow cytometry. Plasma samples were tested for biochemical markers using multi-analyte profile technology. Results: Out of the 148 patients enrolled in the study, 138 were evaluable for immunological analyses. Baseline characteristics were similar in both arms. Day 1 blood samples show: i) a correlation between lower levels of inflammation-associated plasma proteins and a longer median survival in Arm 1 (TG4010 + chemotherapy) (p< 0.001); ii) an improved clinical outcome with TG4010 in patients having normal levels of lymphocytes with an activated NK phenotype. Day 43 blood samples show: i) an association between higher levels of activated T lymphocytes and longer patient survival in Arm 1 (p < 0.05). No such association was observed in patients in Arm 2 (chemotherapy alone); ii) a longer survival for patients with higher levels of Interferon γ in Arm 1 than in Arm 2 (p=0.0001). Patients in both Arm 1 and Arm 2 showed specific binding of MUC1 tetramers to circulating CD8+ lymphocytes. No significant association between either treatment arm or clinical outcome and MUC1 tetramer binding was detected. Conclusions: These results identify the level of activated NK cells at baseline as a predictive biomarker for selection of patients to be treated with TG4010. Biomarker data including Interferon γ support a Th1 dependent pathway of activity for TG4010. [Table: see text] [Table: see text]