Tuesday, May 23, 2000
New Orleans -- May 23, 2000 --Genentech, Inc. (NYSE: DNA) today announced preliminary positive results from two Phase II clinical trials 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 non-small cell lung cancer and as a single agent in metastatic breast cancer.
Data from these studies were presented today at the 36th Annual Meeting of the American Society of Clinical Oncology (ASCO). Additionally, preliminary positive results from a completed Phase II trial in metastatic colorectal cancer were presented on Sunday, May 21, 2000 (see separate Genentech release).
"The Phase II results seen in three solid-tumor cancers are an important milestone for our anti-VEGF clinical development program and our BioOncology initiative," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president of Development and Product Operations and chief medical officer. "We now have further clinical evidence that the potential to block VEGF, the key angiogenic factor in providing tumors with nutrients and oxygen, with our anti-VEGF monoclonal antibody may inhibit certain solid-tumor growth. We are encouraged by these results that indicate anti-VEGF's potential clinical activity both as a single agent and in combination with various chemotherapy regimens."
Phase II Results: Non-Small Cell Lung Cancer (Abstract #1896)
The open-label Phase II investigational study in non-small cell lung cancer, presented by Russell DeVore, M.D., Vanderbilt University, Nashville, Tenn., was conducted in 99 patients previously untreated for advanced metastatic disease. The primary endpoints of response rates and time to disease progression were determined in a blinded fashion by an independent review facility. Survival was also reported. Patients were randomized into one of three treatment arms receiving either anti-VEGF at 7.5 mg/kg (low dose) or anti-VEGF at 15 mg/kg (high dose), every three weeks until disease progression or for one year (up to 18 courses), in combination with carboplatin/paclitaxel, or carboplatin/paclitaxel alone. All patients received carboplatin/paclitaxel every three weeks for six cycles.
The response rate was 21.9 percent (7/32 patients) in the low dose and 40.0 percent (14/35 patients) in the high dose anti-VEGF combination arms, compared to a response rate of 31.3 percent (10/32 patients) in the carboplatin/paclitaxel arm alone.
Time to disease progression was 3.9 months in the low dose and 7.0 months in the high dose combination arms, compared to 6.0 months with carboplatin/paclitaxel alone. Survival results were 11.6 months in the low dose and 17.7 months in high dose combination arms, compared to 14.9 months with carboplatin/paclitaxel alone. Anti-VEGF at the higher dose in combination with chemotherapy appeared to show an increase for all three endpoints compared to chemotherapy alone.
In this Phase II trial, six (of 66) patients treated with anti-VEGF experienced sudden serious pulmonary hemorrhage, four of which resulted in a fatal outcome. This adverse event has not occurred in any of the other clinical trials with anti-VEGF. Four of the six patients with hemoptysis (coughing up blood) had squamous cell carcinoma. Most other adverse events seen in this study were consistent with those of carboplatin/paclitaxel alone. Adverse events seen more often in the combination arms included headache, fever, nosebleeds, hypertension, diarrhea and stomatitis. The majority of these events were Grade 1/2 and all were transient and reversible.
"We developed a comprehensive Phase II clinical trial program that included active control arms in the non-small cell lung and colorectal cancer studies to provide a profile of the potential safety and efficacy of anti-VEGF, as well as important information on the most appropriate dosing regimens," said Dr. Hellmann. "While we are pleased with the Phase II results, Phase III trials in larger patient populations are needed to better understand the potential of anti-VEGF to improve patient outcomes."
Interim Phase II Data: Metastatic Breast Cancer (Abstract #5C)
George Sledge, M.D. of Indiana University, Indianapolis presented interim results of a Phase II investigational open label study of 59 women with relapsed metastatic breast cancer. Overall, anti-VEGF was well tolerated as a single agent. Adverse events that may have been associated with anti-VEGF therapy included hypertension and proteinuria.
The Phase II trial enrolled participants who had all relapsed following at least one chemotherapy treatment for metastatic disease into two cohorts given anti-VEGF either at a 3mg/kg or 10 mg/kg dose. Anti-VEGF was given intravenously every two weeks until disease progression or to a maximum of 13 infusions.
Objective responses to single agent anti-VEGF were seen in five of 59 women (8.5 percent), including one response among 18 patients (5.6 percent) in the 3mg/kg cohort and four responses among the 41 women (9.8 percent) in the 10 mg/kg cohort. One of the five women who responded experienced a complete response and four had partial responses. At the final assessment at 22 weeks, two of 18 (11 percent) patients at 3 mg/kg and eight of 41 (20 percent) patients at 10 mg/kg had either stable disease or an ongoing partial or complete response. Additional cohorts to this Phase II trial are currently being enrolled.
Future Anti-VEGF Clinical trials
Genentech is currently planning to initiate a company-sponsored Phase III clinical trial in colorectal cancer scheduled to begin by the end of the third quarter 2000. The company also is working closely with the Eastern Cooperative Oncology Group (ECOG) to conduct a Phase III clinical trial in non-small cell lung cancer that is scheduled to begin by the end of the year. Both trials will evaluate anti-VEGF in combination with the "standard of care" chemotherapy. In metastatic breast cancer, patients are continuing to be enrolled into the Phase II study evaluating anti-VEGF as a single agent, and additional trials evaluating anti-VEGF in combination with chemotherapy are currently being planned and are expected to begin in the fourth quarter of 2000. A Phase II trial evaluating anti-VEGF as a single agent in renal cell carcinoma (kidney cancer) is ongoing in collaboration with the National Cancer Institute (NCI) and is expected to be completed in 2002. Additionally, we are in discussions with the NCI on future studies with anti-VEGF in a variety of other cancers. Physicians and people interested in anti-VEGF clinical trials in these four cancers should call 1-888-662-6728.
Vascular endothelial growth factor (VEGF) was first discovered by Genentech scientists and 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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