ImClone Systems Incorporated has announced that it has enrolled the first patient in a disease-directed Phase II clinical trial of IMC-1121B to treat patients with advanced hepatocellular carcinoma (liver cancer).
IMC-1121B, an anti-vascular endothelial growth factor receptor-2 (VEGFR-2) monoclonal antibody, is one of a number of proprietary antibodies in ImClone ‘ s robust clinical development pipeline.
This multicenter, multinational, open-label Phase II study of IMC-1121B is enrolling patients with advanced, inoperable liver cancer who have not received prior chemotherapy or other systemic therapies for their disease. A total of 40 patients are expected to be enrolled. The primary objective of the study is to determine the progression-free survival of patients with previously untreated and inoperable liver cancer when treated with IMC-1121B. This Phase II study is designed to evaluate the efficacy, safety and pharmacology of IMC-1121B administered every two weeks by intravenous infusion.
“Recently, targeting malignant angiogenesis has been shown to confer clinical benefit in patients with advanced liver cancer. IMC-1121B represents a potentially ideal therapeutic for treating patients with this cancer due to its high potency in blocking the VEGFR-2, the principal culprit that drives malignant angiogenesis,” said Eric K. Rowinsky, M.D., Executive Vice President and Chief Medical Officer of ImClone. “Additionally, as a monoclonal antibody, IMC-1121B targets the VEGFR-2, thereby minimizing the likelihood of side effects that are noted with many new drugs, particularly the tyrosine kinase inhibitors that may affect many targets in a nonspecific manner.”
“ This Phase II trial is a part of a multipronged clinical development plan consisting of highly rational and strategically designed Phase II and III evaluations of IMC-1121B. We are rolling these out to serve as platforms for subsequent registrational activity, based on preclinical and early clinical results noted to date with ImClone ‘ s anti-VEGFR-2 antibodies, ” said John H. Johnson, Chief Executive Officer of ImClone.
IMC-1121B is a fully human IgG1 monoclonal antibody. It is designed to bind to a specific site on VEGFR-2, a receptor found on tumor vasculature, that results in blocking certain ligands known as vascular endothelial growth factors from binding to and activating the receptor. Anti-angiogenesis approaches, in particular blocking the activation of VEGF pathways, have been shown to be highly effective in treating cancer. IMC-1121B’s unique mechanism of action specifically blocks VEGFR-2 activation, allowing for maximal angiogenesis inhibition. In 2007, ImClone conducted two Phase I studies of IMC-1121B, which demonstrated antitumor activity as a single agent and tolerable safety and pharmacologic profiles when administered either weekly or every two to three weeks. Enrollment in the weekly and every-two-weeks regimens is complete; however, patients continue to receive treatment with IMC-1121B. Enrollment in the every-three-week-regimen continues. In addition to the Phase II study of IMC-1121B in patients with advanced liver cancer, Phase II studies of IMC-1121B in patients with advanced kidney cancer and malignant melanoma have begun to enroll patients.