Sunday, May 21, 2000
New Orleans -- May 21, 2000 --Genentech, Inc. (NYSE: DNA) today announced preliminary positive results from a Phase II trial evaluating the company's investigational recombinant humanized monoclonal antibody to vascular endothelial cell growth factor (rhuMAb-VEGF), or anti-VEGF, in combination with chemotherapy in patients with advanced metastatic colorectal cancer.
Safety and efficacy data in colorectal cancer were presented in an oral presentation at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO). Results from a completed Phase II trial in advanced metastatic non-small cell lung cancer and interim Phase II results in metastatic breast cancer will be presented at ASCO on Tuesday, May 23.
"We are encouraged by these preliminary Phase II results that demonstrate that the addition of anti-VEGF to standard chemotherapy appears to be an active therapy in metastatic colorectal cancer," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president of Development and Product Operations and chief medical officer.
"In this investigational trial, in addition to achieving our primary endpoints, anti-VEGF in combination with chemotherapy appears to have a potential impact on survival in this patient population."
The open-label Phase II study (abstract #939) in metastatic colorectal cancer, presented today by Emily Bergsland, M.D. of the University of California, San Francisco (UCSF) was conducted in 104 patients previously untreated for advanced metastatic disease. Patients were randomized into one of three treatment arms receiving either anti-VEGF at 5 mg/kg (low dose) or anti-VEGF at 10 mg/kg (high dose), every two weeks until disease progression, in combination with 5-FU/leucovorin chemotherapy, or 5-FU/leucovorin alone. All patients received 5-FU/leucovorin weekly for six weeks of an eight-week cycle ongoing until disease progression or a maximum of one year.
The primary endpoints of response rates and time to disease progression were determined in a blinded fashion by an independent review facility. Survival also was evaluated. The response rates were 40 percent (14/35 patients) in the low dose and 24 percent (8/33 patients) in the high dose anti-VEGF combination arms, compared to a response rate of 17 percent (6/36 patients) in the 5-FU/leucovorin alone arm.
Time to disease progression was 9.0 months in the low dose and 7.2 months in the high dose combination arms, compared to 5.2 months in the 5-FU/leucovorin alone arm. Median survival has not yet been reached at 17.3 months in the low dose anti-VEGF combination arm, and was 16.1 months in the high dose combination arm, compared to 13.6 months in the 5-FU/leucovorin alone arm.
Anti-VEGF was generally well tolerated and adverse events were primarily those expected with 5-FU/leucovorin chemotherapy. Some mild to moderate adverse events that appeared more in the anti-VEGF arms than with chemotherapy alone included fever, chills, headache, hypertension, infection and rash. Nosebleeds occurred in 16 of 35 patients in the low dose arm and 17 of 32 patients in the high dose arm (five of 35 in 5-FU/leucovorin alone arm).
There were 13 reported incidents of thrombosis (nine in the low dose arm and four in the high dose arm) that may have been attributed to anti-VEGF. Thrombosis is known to be a complication of cancer and the treatment of cancer. No patients developed antibodies to anti-VEGF.
Phase III Trial in Colorectal Cancer
Genentech is currently planning a company-sponsored Phase III trial in colorectal cancer evaluating anti-VEGF as first-line therapy in combination with the "standard of care" chemotherapy. The company is currently working with the investigators and is in discussions with the U.S. Food and Drug Administration (FDA) regarding the study design criteria. Genentech expects to initiate the Phase III trial by the end of the third quarter 2000. The company is also planning to initiate an additional Phase II trial evaluating 5-FU/leucovorin alone vs. 5-FU/ leucovorin with anti-VEGF that is scheduled to begin by the end of the second quarter 2000. Physicians and people with colorectal cancer interested in anti-VEGF clinical trials should call 1-888-662-6728.
"As we begin the steps of finalizing our Phase III trial design, we are looking forward to continuing our comprehensive clinical development program in colorectal cancer that will provide us with a better understanding of the potential safety and efficacy of anti-VEGF in a larger patient population," said Dr. Hellmann.
Vascular endothelial growth factor (VEGF), which was first discovered by Genentech scientists, is a protein that is secreted from ischemic (tissue lacking oxygen) cells, including those that are malignant or cancerous. VEGF stimulates new blood vessel formation, or angiogenesis, by binding to specific receptors on nearby blood vessels to stimulate extensions to existing blood vessels.
Research has shown that angiogenesis, by supplying blood to tumors, plays an important role in both tumor growth and metastasis. Once VEGF was identified, Genentech scientists developed a humanized monoclonal antibody, anti-VEGF, that in preclinical research was shown to bind to VEGF and thereby prevent it from binding to its receptors.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Thirteen of the approved products of biotechnology stem from Genentech science. Genentech markets seven products directly in the United States. The company has headquarters in South San Francisco, California, and is traded on the New York Stock Exchange under the symbol DNA.
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