Abstract
5530 Background: The fully human IgG1κ monoclonal antibody 2F8 (HuMax-EGFr) targets the EGFR. 2F8 competitively inhibits ligand binding and ligand-induced receptor phosphorylation and it induces significant antibody-dependent cellular cytotoxicity in vitro. Methods: A phase I/II single dose escalation study followed by a repeat dose extension. 24 patients with histologically confirmed recurrent or metastatic SCCHN received i.v. infusions in doses of 0.15, 0.5, 1, 2, 4, or 8 mg/kg. Four patients were included at each dose level. At day 28 the single dose was followed by 4 weekly infusions at the same dose. The primary objective was safety. Efficacy was evaluated by FDG-PET and by CT-scans one week after last dose. Results: Data is presented from 24 patients. 6 patients were withdrawn prior to repeated dosing due to disease progression. No patients experienced dose limiting toxicities and maximum tolerated dose has not been reached. The frequency of acneiform rashes increased with dose. Hence, 7 of 8 patients receiving 4 or 8 mg/kg experienced rash. At these 2 dose levels, pharmacokinetic data showed constant clearance indicating saturation of compartments. Response evaluation by FDG-PET in 15 evaluable patients showed 6 partial metabolic responses (PMR) and 3 stable metabolic disease (SMD), all occurring in the 2, 4, and 8 mg/kg dose groups. In fact, all 8 patients at 4 or 8 mg/kg obtained PMR or SMD. Response evaluation by CT in 16 evaluable patients showed 2 patients with partial response and 8 with stable disease all occurring in the 1, 2, 4, and 8 mg/kg dose group. 6 out of 7 patients treated with 4 or 8 mg/kg thus obtained partial response or stable disease. Conclusions: 2F8 has a favorable safety profile in doses up to 8 mg/kg. Encouraging efficacy data using FDG-PET and CT imaging are demonstrated, particularly in the 4 and 8 mg/kg dose groups. The study is currently extended at the 8 mg/kg dose level. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genmab Genmab
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call