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

Abstract 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/mm3 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.