ImClone Systems Incorporated (NASDAQ: IMCL), a global leader in the development and commercialization of novel antibodies to treat cancer, today announced that its disease-directed randomized Phase 2 clinical trial of IMC-A12 in patients with previously treated HER2-expressing locally advanced or metastatic breast cancer has commenced patient enrollment. IMC-A12 is ImClone’s fully human, IgG1 anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody.

The primary objective of this Phase 2 study is to evaluate the antitumor activity of the combination of capecitabine and lapatinib with and without IMC-A12 in patients with HER2-expressing Stages IIIB, IIIC, or IV breast cancer that has progressed on trastuzumab-containing treatment. This study is being conducted by the North Central Cancer Treatment Group (NCCTG), a national clinical research group sponsored by the National Cancer Institute (NCI). NCCTG is comprised of a network of more than 1,000 community-based cancer treatment clinics in the United States, Canada and Mexico that work with Mayo Clinic to conduct clinical studies for advancing cancer treatment. Other Cooperative Groups are assisting NCCTG to recruit patients, via the CTSU (NCI’s CANcer Therapy Study Unit). This study is one of at least 10 Phase 1 and 2 clinical trials of IMC-A12 sponsored by the Cancer Therapy Evaluation Program (CTEP) of the Division of Cancer Treatment and Diagnosis (DCTD), NCI. ImClone announced the selection of these proposals by NCI in September 2007.

“This study of IMC-A12 is a rationally designed study based on preclinical evidence suggesting that there are interactions between the HER2 and IGF-IR that may be exploited to improve treatment outcome for women with HER2-expressing breast cancer,” said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone. “The NCCTG is seeking to determine if the anticancer activity of the combination with lapatinib and capecitabine, which is an approved treatment for women with HER2-expressing breast cancer that is no longer responsive to trastuzumab, can be improved by the addition of IMC-A12.”

This Phase 2 study of IMC-A12 will enroll approximately 154 patients at more than 140 sites across the U.S. Patients will be randomized to receive treatment with either capecitabine and lapatinib (one-third of the patients) or the same treatment plus IMC-A12 (two-thirds of the patients). Treatment in both arms will be continued as long as potential benefit is shown. The primary endpoint of the study is progression-free survival.

“Research asserts that HER2-positive breast tumors may resort to the IGF-1R pathway as an adaptive growth mechanism to therapies that target the HER2 cell proliferation mechanism,” said Paul Haluska, M.D., Ph.D.