Abstract 258: A phase I study of the novel high affinity VEGF blocker VEGF trap in patients with refractory solid tumors and lymphoma
Citation: European Journal of Cancer Vol 38, Suppl. 7, November 2002, page 81
J. Dupont1, S. Pezzulli1, M. Gordon2, D. Mendelson2, J. Murren3, A. Hsu3, J. Holash4, N. Stahl4, J. Cedarbaum4, D.R. Spriggs1
1Memorial Sloan-Kettering Cancer Center, Medicine, New York, USA; 2University Of Arizona, Medicine, Phoenix, USA; 3Yale University, Medicine, New Haven, USA; 4Regeneron Pharmaceuticals Inc., Tarrytown, USA
VEGF Trap is a fusion protein consisting of portions of the human Vascular Endothelial Growth Factor (VEGF) receptor VEGFR1 (flt-1) and VEGFR2 (KDR) extracellular domains fused in series to the Fc portion of human IgG1. It acts by binding and inactivating VEGF in the circulation and in tissues. VEGF Trap has substantially greater (1-5 pM) affinity for the VEGF ligand than monoclonal antibodies. Preclinical studies indicate that subcutaneously (sc) administered VEGF Trap can substantially inhibit the growth of a variety of tumors implanted in mice. Preclinical pharmacokinetics predicted a half-life compatible with weekly dosing in humans. In this open-label, dose-escalation phase 1 study, a single sc dose of VEGF Trap is given to patients with relapsed and refractory solid tumors and lymphoma followed 4 weeks later by 6 weekly (sc) doses of the drug. Samples for pharmacokinetic analysis are collected both after the single dose and during chronic treatment. Patients are monitored for the development of anti-VEGF Trap antibodies. Anti-tumor efficacy is assessed by measuring changes in tumor mass clinically and/or by MRI. Tumor perfusion and water content is assessed in a subset of patients by dynamic contrast (Gadolinium)- enhanced MRI techniques. To date 6 patients have been treated on two dose levels: 25mcg/kg and 50mcg/kg. Early data reveals that the VEGF Trap complexes to circulating VEGF in plasma. To date, no anti-VEGF Trap antibodies have been detected in any of the patients treated. Longer term results for a larger number of patients and the pharmacokinetics of the Trap and Trap:VEGF complexes will be discussed. |
