First-in-human phase I study of CetuGEX, a novel anti-EGFR monoclonal antibody (mAb) with optimized glycosylation and antibody dependent cellular cytotoxicity.

3008 Background: Epidermal growth factor receptor (EGFR) is a validated target in cancer. EGFR antagonists in clinical use do not exploit the full potential of this target. CetuGEX is an IgG1 mAb against EGFR. Fully human and optimized glycosylation lead to a 10- to 250-fold improvement of ADCC-mediated tumor cell killing in all FcγRIIIa allotypes and lack of immunogenic carbohydrate-chains, compared to cetuximab. Methods: Eligible patients with advanced solid tumors, progressing after standard treatment, were enrolled into this phase I, first-in-human, multicenter, single agent dose escalation trial. PK, PD and immunological parameters were assessed. Endpoints were safety and tolerability and secondarily pharmacokinetics, immunogenicity and anti-tumor activity. Results: 41 patients were treated on a q1w (8 dose levels from 12 to 1,370 mg flat dose), or q2w (990 mg flat) schedule. 25 pts had received at least 8 weekly doses (per protocol population [PP]).The most frequently observed drug-related AE were n...