Open-label, multicentre expansion cohort to evaluate imgatuzumab in pre-treated patients with KRAS-mutant advanced colorectal carcinoma

Aim: Imgatuzumab (GA201) is a novel anti-epidermal growth factor receptor (anti-EGFR) antibody glycoengineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the efficacy of imgatuzumab in patients with EGFR-positive, KRAS-mutant advanced colorectal cancer. Methods: Patients received single-agent imgatuzumab (1400 mg on day 1 and 8 followed by q2W) as third line therapy in an open-label, multicentre, non-randomised, expansion study. The primary end-point was tumour response. Pre- and on-treatment biopsies and blood samples were investigated for biomarkers related to imgatuzumab's believed mechanism of action (MoA). Results: 25 patients were treated and the best overall response was stable disease occurring in 40% of patients at 8 weeks, 24% at 16 weeks and 8% (two patients) at 32 weeks. Median overall survival was 9.3 months (95% confidence interval (CI): 5.1-12.3). Treatment-related rash, hypomagnesaemia and infusion-related reactions were the most common adverse events. Comparison of pre- and post-treatment biopsies revealed that the number of tumour-infiltrating immune cells increased notably after one cycle of therapy (median compound immune reactive score of 1491 versus 898 cells/mm(3) at baseline), whereas the number of peripheral natural killer cells decreased. A potential association between baseline tumour immune infiltration and clinical efficacy was seen. Conclusions: These data may suggest that the MoA of imgatuzumab involves ADCC-related immune effects in the tumour and is not limited to simple receptor blockade. (C) 2013 Elsevier Ltd. All rights reserved.