BAY 43-9006, a novel RAF kinase and VEGFR inhibitor under investigation for the prevention of tumor growth, combines two anticancer activities: inhibition of tumor cell proliferation and tumor angiogenesis.
"In this study, the use of BAY 43-9006 in patients with renal cell carcinoma has resulted in a high level of durable disease stabilization or tumor shrinkage," said lead investigator Mark Ratain, M.D., Professor of Medicine and Associate Director for Clinical Sciences, Cancer Research Center, University of Chicago, USA. "As we continue to evaluate BAY 43-9006, I am excited about the potential it may offer in the fight against this form of kidney cancer."
The data included tumor response for 89 participants (of 106 total RCC patients) who were assessed at 12 weeks, as well as duration of response data for 37 of these participants who experienced tumor shrinkage of greater than 25 percent. Thirteen of the participants had their tumors shrink by at least 50 percent at the 12-week assessment. Nine patients were confirmed to have this degree of tumor response by subsequent scans conducted at least six weeks later. Thirty-eight participants had disease stabilization and were randomized. The remaining 31 (of 106) participants had disease progression or were discontinued from the study for other reasons.
The entire group of 37 patients who had tumor shrinkage, and continued to receive BAY 43-9006 in the open-label phase of the study, had an estimated median time to tumor progression (TTP) of 48 weeks based on investigator assessment. Of these, 88 percent were progression free at six months. These investigator-reported data, including the confirmatory radiology scans needed to define response rates, are subject to a final independent radiologic review, which will be completed by the sponsor at the conclusion of the study.
Over 85 percent of the study participants with RCC had tumors that progressed despite at least one prior systemic treatment, and all patients had progressive disease on study entry. The RCC participants were part of a larger study population consisting of 484 treated patients with advanced refractory solid tumors of multiple types. Safety data were collected for all tumor types. In the study, the most commonly reported drug-related events include mild-to-moderate hand-foot syndrome, rash, diarrhea, and hypertension, which were shown to be manageable and reversible.
"The analysis of the RCC patient experience in this Phase II study is expected to be complete in the second half of the year," said Susan Kelley, M.D., vice president, Oncology, Bayer Pharmaceuticals Corporation. "We remain encouraged by these early findings, and are very pleased that enrollment in the ongoing worldwide Phase III RCC study is proceeding well, with virtually all trial sites open and actively accepting patients."
Phase II Study Design
The BAY 43-9006 Phase II multi-center, randomized discontinuation trial, which enrolled more than 200 RCC patients, uses a study design that consists of two stages: a 12-week induction phase followed by a randomization phase and a parallel BAY 43-9006 open-label phase. During the first stage, all study participants received BAY 43-9006 orally at 400 mg twice a day. Subsequently, those patients whose tumor burden was within 25 percent of their pretreatment measurements were randomized to either BAY 43-9006 or placebo for another 12 weeks of treatment. At its conclusion, the codes will be broken on the randomized patients to evaluate possible evidence of the compound's contribution to the disease stabilization of these patients. Additionally, those patients who had tumor shrinkage of more than 25 percent at the week 12 evaluation continued to be treated with open-label BAY 43-9006 after the initial 12-week stage. Patients who had tumor growth of 25 percent or more were discontinued from the study.
About BAY 43-9006
BAY 43-9006, a novel investigational drug candidate, demonstrated both anti-proliferative and anti-angiogenic properties - two important anticancer activities. In preclinical models, BAY 43-9006 inhibited tumor cell proliferation by targeting the RAF/MEK/ERK signaling pathway at the level of RAF kinase. BAY 43-9006 also exerted an antiangiogenic effect by targeting the receptor tyrosine kinases VEGFR-2 and PDGFR and their associated signaling cascades.
For more information on BAY 43-9006 clinical trials, visit www.clinicaltrials.gov
Additional BAY 43-9006 ASCO Data
Additional BAY 43-9006 data being presented at this year's ASCO meeting include:
- Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity in the expansion cohort of patients with metastatic melanoma. Keith T. Flaherty, MD. Abstract #7507 (Oral Presentation)
- BAY 43-9006 in patients with advanced melanoma: The Royal Marsden experience. Tanya Ahmad, MRCP. Abstract #7506 (Oral Presentation)
- A phase I/II trial of BAY 43-9006 and gemcitabine in advanced solid tumors and in advanced pancreatic cancer. Lillian L. Siu, MD. Abstract #3059 (Poster #M9)
- Results of a phase I trial of BAY 43-9006 in combination with doxorubicin in patients with refractory solid tumors. Heike Richly, MD. Abstract #3049 (Poster #L10)
- A randomized phase I clinical and biologic study of two schedules of BAY 43-9006 in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): A National Cancer Institute of Cancer Clinical Trials Group Study. Michael Crump, MD. Abstract #6611 (Poster # L11)
- Pharmacodynamic study of the RAF kinase inhibitor BAY 43-9006: Mechanisms of hypertension. Maria Luisa Veronese, MD. Abstract #2035 (Poster #25)
- Results of a phase I trial of BAY 43-9006 in combination with oxaliplatin in patients with refractory solid tumors. Petra Kupsch, MD. Abstract #3056 (Poster #M6)
Renal cell carcinoma is the most common form of kidney cancer. Nearly 190,000 people worldwide are diagnosed (about 31,000 Americans) with renal cell carcinoma each year, and more than 91,000 of them die (about 12,000 Americans) from the disease annually. For more information on renal cell carcinoma, visit the Kidney Cancer Association (KCA) web site at: www.kidneycancerassociation.org.
About Onyx Pharmaceuticals, Inc.
Onyx Pharmaceuticals, Inc. is engaged in the development of novel cancer therapies that target the molecular basis of cancer. With its collaborators, the company is developing small molecule drugs, including BAY 43 9006 with Bayer Pharmaceuticals Corporation. For more information about Onyx's pipeline and activities, visit the company's web site at: www.onyx-pharm.com.
About Bayer Pharmaceuticals Corporation
Bayer Pharmaceuticals Corporation (www.bayerpharma.com) is part of the worldwide operations of Bayer HealthCare AG, a subgroup of Bayer AG.
Bayer HealthCare, with sales of approximately 8.9 billion Euro in 2003, is one of the world's leading, innovative companies in the health care and medical products industry.
The company combines the global activities of the divisions Animal Health, Biological Products, Consumer Care, Diagnostics and Pharmaceuticals. About 34,600 people are employed by Bayer HealthCare worldwide.
Our aim is to discover and manufacture innovative products that will improve human and animal health worldwide. Our products enhance well being and quality of life by diagnosing, preventing and treating disease.
Forward Looking Statements
This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer Group management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports filed with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including its Form 20-F). Bayer assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.
This news release also contains "forward-looking statements" of Onyx within the meaning of the federal securities laws. These forward-looking statements include without limitation, statements regarding the timing, progress and results of the clinical development, regulatory processes and commercialization efforts of BAY43-9006. These statements are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated. Reference should be made Onyx's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 15, 2004 under the heading "Additional Business Risks" for a more detailed description of such factors. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date of this release. Onyx undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date of this release except as required by law.
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