ImClone Systems Incorporated (NASDAQ:IMCL) and Bristol-Myers Squibb Company (NYSE:BMY) today announced results from two randomized Phase III trials of ERBITUX(R) (cetuximab) in patients with metastatic colorectal cancer. These are the first large, randomized studies to examine the impact of ERBITUX treatment on overall survival in colon cancer.
A randomized, multicenter, Phase III trial (NCIC CTG CO.17) compared ERBITUX plus best supportive care to best supportive care alone in 572 patients with metastatic colorectal cancer whose disease was refractory to all available chemotherapy, including irinotecan, oxaliplatin, and fluoropyrimidines. The study, conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG), met its primary efficacy endpoint showing a statistically significant improvement in overall survival. These are the first data of an anticancer therapy to demonstrate overall survival in this refractory treatment setting. The NCIC CTG is scheduled to submit the data from this study for presentation at a major medical meeting in 2007.
“This is the second tumor type where ERBITUX has shown survival benefit,” said Eric Rowinsky, M.D., Chief Medical Officer and Senior Vice President of ImClone Systems. “Additionally, no other EGFR-targeted therapy has demonstrated an improvement in overall survival in a Phase III colorectal cancer clinical study.”
A second Phase III, randomized study, known as the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC), compared irinotecan to irinotecan plus ERBITUX in approximately 1,300 patients whose disease was not responding to first-line oxaliplatin-based chemotherapy. After randomization, patients were treated until their disease progressed. Upon disease progression, study treatment was stopped and further treatment was at the discretion of the physician.
Secondary efficacy endpoints (progression free survival, response rate) strongly favored the combination of ERBITUX plus irinotecan over irinotecan alone; however, the primary endpoint (overall survival) was not met.
Efforts to interpret these confounded results are ongoing. A preliminary review of the data reveal that a considerable number of patients randomized to the irinotecan arm went on to receive ERBITUX with or without irinotecan after failing irinotecan alone.
“The studies provide important new information for patients with advanced colorectal cancer, and are part of our comprehensive clinical development program designed to fully understand the potential uses of ERBITUX for cancer patients,” said Martin Birkhofer, M.D., Vice President, Oncology Global Medical Affairs, Bristol-Myers Squibb. “We look forward to our full analysis of the data, and to sharing the results with the scientific community at a major medical meeting.”
“We are encouraged by the totality of the results from both studies and we plan to have discussions with the Food and Drug Administration concerning a registrational submission,” said Eric Rowinsky, M.D. Chief Medical Officer and Senior Vice President of ImClone Systems.
About ERBITUX(R) (Cetuximab)
ERBITUX is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumor cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of ERBITUX to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, ERBITUX can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. While the mechanism of ERBITUX’ anti-tumor effect(s) in vivo is unknown, all of these processes may contribute to the overall therapeutic effect of ERBITUX. EGFR is part of a signaling pathway that is linked to the growth and development of many human cancers, including those of the head and neck, colon and rectum.
ERBITUX (Cetuximab), in combination with radiation therapy, is indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. ERBITUX as a single agent is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed.
ERBITUX is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma (mCRC) in combination with irinotecan for patients who are refractory to irinotecan-based chemotherapy, and as a single agent for patients who are intolerant to irinotecan-based therapy. The effectiveness of ERBITUX for the treatment of EGFR-expressing mCRC cancer is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX for the treatment of EGFR-expressing mCRC.
About Colorectal Cancer
In the U.S., approximately 149,000 people will be diagnosed with cancer of the colon or rectum this year. Half of these patients have metastatic disease, or cancer that has spread to other organs, at the time of diagnosis. EGFR is expressed in up to 77.7 % of colorectal cancer tumors. Colorectal cancer is the third most common cancer in both men and women.(1)
About ImClone Systems
ImClone Systems Incorporated is committed to advancing oncology care by developing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. The Company’s research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone Systems’ strategy is to become a fully integrated biopharmaceutical company, taking its development programs from the research stage to the market. ImClone Systems’ headquarters and research operations are located in New York City, with additional administration and manufacturing facilities in Branchburg, New Jersey.
About Bristol-Myers Squibb
Bristol-Myers Squibb is dedicated to the discovery, development and exhaustive exploration of innovative cancer fighting therapies designed to extend and enhance the lives of patients living with cancer. More than 40 years ago, Bristol-Myers Squibb built a unified vision for the future of cancer treatment. With expertise, dedication and resolve, that vision led to the development of a diverse global portfolio of anti-cancer therapies that are an important cornerstone of care today. Hundreds of scientists at Bristol-Myers Squibb’s Pharmaceutical Research Institute are studying ways to improve current cancer treatments and identify better, more effective medicines for the future.
Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.