A phase I study of an anti-epidermal growth factor receptor monoclonal antibody for the treatment of malignant gliomas

OBJECTIVE: Epidermal growth factor receptor (EGFR) is an operationally specific antigen in malignant gliomas; it is overexpressed in > 60% of these tumors, whereas its expression is very low in normal brain. This study aimed to evaluate whether an adequate amount of an anti-EGFR monoclonal antibody (MAb) could reach a tumor after a single intravenous administration. METHODS: This study was open, nonrandomized, and uncontrolled. Single doses (20, 40, 100, 200, or 400 mg) of the murine MAb EMD55900 (MAb 425) were administered intravenously before surgery to 30 patients with malignant brain tumors. Serum samples were taken at defined time intervals during infusion, to determine EMD55900 concentrations, and 10, 21, and/or 42 days after infusion, to evaluate the development of human anti-mouse antibodies. Tumor samples were investigated for EGFR and EMD55900 contents. RESULTS: Tolerance to EMD55900 was good. Increased liver transaminase levels were noted for three patients with Grade 1 toxicity. Twenty patients developed significant human anti-mouse antibody titers, without correlation with the administered dose. The median half-life of EMD55900 in serum ranged from 6 hours for 20 mg to 24 hours for 400 mg. In the membrane fractions of the tumors, EGFR saturation by EMD55900 varied with the injected dose of MAb. No binding was detected after a 20-mg dose. After doses of 40, 100, 200, and 400 mg, the mean saturation levels were 33, 73, 89, and 71%, respectively. CONCLUSION: This study indicates that a single intravenous administration of EMD55900 is well tolerated and produces substantial in vivo tumor binding with doses > 100 mg.