Final Data from Phase I Single-Agent Studies also Presented
SOURCE: Bayer Pharmaceuticals Corporation; Onyx Pharmaceuticals, Inc.
Novel RAF Kinase Inhibitor Bay 43-9006 Shows Early Signs of Tolerability and Activity in Phase Ib Combination Trials Reported at ASCO
WEST HAVEN, Conn. and RICHMOND, Calif., June 2 - Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc. today announced at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago encouraging Phase Ib data from two clinical trials of BAY 43-9006, a novel, investigational RAF kinase inhibitor, in combination with standard chemotherapeutics, as well as final Phase I results that confirm and extend the positive findings presented at international medical meetings in 2002. This novel inhibitor is an orally active small molecule agent currently in Phase II clinical development in a collaboration between Bayer and Onyx. The data describe safety findings and preliminary antitumor activity from multiple Phase Ib chemotherapy combination trials and Phase I single-agent clinical trials.
Phase Ib Clinical Study: BAY 43-9006 in Combination with Gemcitabine (Abstract 828)
Safety, pharmacokinetics and tumor response rate from a multicenter Phase Ib study of BAY 43-9006 in combination with gemcitabine were presented today in a poster presentation by Lillian L. Siu, M.D., of Princess Margaret Hospital in Toronto, Canada. The study was a dose-escalating Phase Ib trial, in which BAY 43-9006 was administered continuously at three different dose levels up to 400 mg twice daily, along with gemcitabine given at the standard dose of 1000 mg/m2. The patients had advanced solid tumors including pancreatic, colorectal, ovarian, esophageal, gastric, liposarcoma, nasopharyngeal and mesothelioma, for which no standard therapy exists and who were deemed suitable for treatment with gemcitabine chemotherapy. The safety results were reported in 20 patients treated on study. Hematological toxicities observed in the clinical data were non-dose limiting and consistent with gemcitabine effects. Non-hematological toxicities included decreased appetite, fatigue, hand-foot syndrome, skin rash, nausea and diarrhea. Only fatigue proved dose-limiting in one patient treated at the highest dose. Preliminary pharmacokinetic analysis revealed no significant interactions between BAY 43-9006 and gemcitabine. Data from 20 patients included one patient with a confirmed partial response in previously treated ovarian cancer, and disease stabilization of eight weeks or more in 11 patients with tumor types including: ovarian, pancreatic, colorectal, nasopharyngeal, and an unknown primary tumor. An expanded cohort of pancreatic cancer patients is currently being evaluated in this study.
Phase Ib Clinical Study: BAY 43-9006 in Combination with Carboplatin and Paclitaxel (Abstract 2854)
Data from a second chemotherapy combination Phase Ib study of BAY 43-9006 were presented Saturday, May 31, at an ASCO session devoted to melanoma and described in an announcement issued that day by the University of Pennsylvania. The multicenter, dose-escalating trial was designed to evaluate different dosage levels of BAY 43-9006 administered in combination with carboplatin and paclitaxel. Thus far, 20 patients with a variety of tumor types have been treated in the study. In an oral presentation, Keith T. Flaherty, M.D., of the University of Pennsylvania reported that BAY 43-9006 was well tolerated when combined with full dose carboplatin and paclitaxel. Toxicities, including skin rash and hand-foot syndrome, resolved themselves. No pharmacokinetic interaction between BAY 43-9006 and paclitaxel or carboplatin was reported. Dr. Flaherty reported confirmed partial responses in three of ten evaluable patients with melanoma, and disease stabilization in six additional melanoma patients, four of whom showed evidence of tumor necrosis.
"These trials are two of eight ongoing studies evaluating BAY 43-9006 in combination with a range of standard chemotherapeutic agents," stated Susan Kelley, M.D., Vice President of Oncology Product Development at Bayer Pharmaceuticals. "Further evaluation of BAY 43-9006 administered in combination with these cytotoxic drugs is warranted, based on these preliminary data. We are encouraged by the non-overlapping toxicity profiles and early indications of activity in the clinical setting."
Phase I Clinical Trials: Single-Agent BAY 43-9006 (Abstract 793)
Final data from single-agent Phase I clinical trials of BAY 43-9006 were presented today in a poster session by Dirk Strumberg, M.D., of the West German Cancer Center at the University of Essen. This report included data from four clinical Phase I single agent studies conducted at the University of Essen, the Jules Bordet Institute in Belgium, the Hamilton Regional Cancer Centre and Princess Margaret Hospital in Canada, and the Dana Farber Cancer Institute and the University of Southern California in the United States. In an analysis of 118 patients with advanced malignancies who received BAY 43-9006 doses of 200 mg twice daily or higher, 29 patients remained on BAY 43-9006 for more than six months, with no tumor progression or serious treatment-related adverse events. Of these, nine were on treatment for more than one year, with no disease progression or serious treatment-related adverse events. Durable partial responses were also observed in one liver cancer patient and one kidney cancer patient. Most of the dose-limiting toxicities were seen at dose levels of 600 mg twice daily or greater and included diarrhea and skin toxicity.
"These results from our now-completed single-agent Phase I program for BAY 43-9006 show signs of a favorable safety profile and preliminary antitumor activity," stated Dr. Kelley. "Phase II clinical trials are ongoing, and we are making preparations for the start of phase III."
About BAY 43-9006
BAY 43-9006 is a novel investigational compound directed against a specific molecular target involved in excess growth signaling in cancer. BAY 43-9006 blocks the enzyme RAF kinase, which is a critical component of the RAS pathway -- an important cascade of chemical signals that control cell division. Activating mutations of a RAS gene are estimated to occur in almost one-third of human cancers, including 90 percent of pancreatic cancer, 50 percent of colon cancer and 30 percent of non-small cell lung cancer. In addition, recent research suggests that a specific RAF kinase, BRAF, is activated by mutation in two-thirds of melanomas and smaller percentages of several other cancers.
Related: Kinase inhibitors in cancer therapy
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