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| |  A New Monoclonal Antibody, VEGF Inhibitor Is Active in Patients with Advanced Solid Tumours: Presented at AACR-NCI-EORTC By Crina Frincu-Mallos, PhD SAN FRANCISCO, CA -- November 1, 2007 -- A novel vascular endothelial growth factor (VEGF) inhibitor, IMC-1121B, showed antitumour activity in 60% of the patients with advanced solid cancers in a phase 1 trial, researchers reported here at the 2007 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. IMC-1121B is a fully human IgG monoclonal antibody, potent against angiogenesis as well as tumour growth and metastasis. It is thought to act by binding to the VEGF ligand, explained the investigators. The lead author, Jennifer L. Spratlin, MD, University of Colorado Cancer Center, Aurora, Colorado, United States, presented the results in a poster session here. This multicentre, first-in-human trial enrolled a total of 37 patients (male to female ratio 23:14), median age 56 years (range, 36 to 76 years). Dr. Spratlin and colleagues aimed to examine the toxicity profile and to determine the maximum tolerated dose (MTD) of IMC-1121B in patients with advanced solid tumours. Patients with a wide variety of cancers were included in the study, the most common being colorectal (n = 6), head and neck (n = 4), pancreatic (n = 3), hepatocellular (n = 3), ovarian cancer (n = 2), and melanoma (n = 2). Patients with prior bevacizumab therapy were ineligible, said the investigators. IMC-1121B was administered intravenously once a week for 4 weeks during a 6-week cycle. A total of 7 dose levels were tested, starting with 2 mg/kg and going up to 16 mg/kg. A dose limiting toxicity (DLT) was initially seen in patients treated with the investigational agent at 8 mg/kg dose level and consisted in a grade 3 hypertension combined with a grade 3 headache, noted Dr. Spratlin. Another grade 3 hypertension DLT occurred when the IMC-1121B dose was increased to 10 mg/kg, followed by an additional grade 3 hypertension and a grade 3 deep vein thrombosis at 16 mg/kg dose level. All these adverse events (AEs) were considered by the investigators to be possibly related to the study agent. The two DLTs observed at the 16 mg/kg dose resulted in closing the study to accrual, in addition to defining 13 mg/kg as the MTD, explained the investigators. The serum samples tested 168 hours after IMC-1121B infusion show an increase in VEGF levels of 1.5 to 3.5 fold relative to the baseline, for all dose levels. Dr. Spratlin and colleagues attributed the elevated VEGF serum concentrations to the displacement of the protein by the drug. A total of 18 patients (49%) had stable disease (SD) as their best response to the IMC-1121B therapy, with 7 patients having SD for more than 6 months. In addition, 4 patients (11%) experienced partial responses (PRs). IMC-1121B is currently in the developmental pipeline at ImClone Systems Incorporated, Branchburg, New Jersey, United States. A phase 2 trial of IMC-1121B in renal cell cancer has started accruing patients, according to the investigators.
[Presentation title: A phase I, pharmacological and biological study of weekly IMC-1121B, a recombinant human IgG1 monoclonal antibody (MAb), targeting vascular endothelial growth factor receptor 2 (VEGFR-2), in patients (pts) with advanced solid tumors. Abstract A33]
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