Exelixis Initiates Phase II Trial Of XL880 In Patients With Gastric Cancer
The multi-center open-label Phase II study will be conducted at multiple clinical sites and enroll patients with metastatic, poorly differentiated diffuse gastric cancer, a tumor type that is associated with amplification of the MET gene. The primary objectives of the study are to determine best- confirmed response rate and to evaluate safety and tolerability of XL880 administered orally for five consecutive days every two weeks. Secondary objectives are to assess progression-free survival, overall survival, duration of response, and to continue characterizing the pharmacokinetic and pharmacodynamic profiles of XL880.
"The Phase II development program for XL880 has been designed to exploit activating genetic changes in the compound's target that occur in a variety of tumor types," said Michael Morrissey, Ph.D., executive vice president of discovery at Exelixis. "Activation of MET by mutation or amplification is associated with disease progression and poor prognosis in a significant number of patients with papillary renal cell carcinoma, gastric cancer, and head and neck cancer. XL880 has demonstrated potent inhibition of MET and other critical drivers of cancer in preclinical studies.
In particular, preclinical experiments have shown that gastric cancer cell lines carrying amplifications of the MET gene are extremely sensitive to the growth inhibitory effects of XL880, providing a strong rationale for testing the clinical utility of the compound in this indication. We are applying this biology-based development approach to all the compounds in our diverse pipeline, matching their specific target inhibition characteristics to the unique molecular profiles of various cancers."
Data from a Phase I trial of XL880 were presented most recently in November 2006 at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. As of October 6, 2006, 40 patients had been enrolled in the Phase I trial and were evaluable for safety; 29 of these were also evaluated for XL880 pharmacokinetics. As reported by the investigators, four patients have had partial responses (papillary renal cell carcinoma [3] and Hurthle cell carcinoma [1]); four patients have had minimal responses (carcinoid [1], colorectal [1], melanoma [1] and medullary thyroid [1]); and seven patients have had stable disease for 3 to 7 months (colorectal [3], renal cell [1], billiary [1], urethral [1] and thyroid [1]).
Additionally, analysis of biopsy samples taken from a patient with melanoma who had stable disease indicated that XL880 inhibited the activation of the RTKs MET and RON, decreasing the activity of the downstream proteins ERK and AKT, which translated into an overall decrease in tumor cell proliferation and an increase in apoptosis in the tumor sample. Similar results have also been observed in tumor biopsies from patients with metastatic breast cancer and medullary thyroid carcinoma. These changes were not observed in samples of normal tissue taken from the same patient.
About XL880
XL880 is an orally bioavailable small molecule compound designed to target multiple RTKs implicated in the development, progression, and spread of cancer. The primary targets of XL880 are the hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, although platelet-derived growth factor receptor (PDGFR), RON, c-KIT, FLT3, and Tie-2 are also inhibited. Activation of MET by mutation or overexpression has been documented as a negative prognostic indicator in patients with various carcinomas, including gastric carcinomas. Activation of MET by mutation is the causative factor in an inherited kidney cancer syndrome, hereditary papillary renal cell carcinoma. Mutational or constitutive activation of MET has also been found in sporadic kidney cancer, lung carcinomas, and head and neck carcinomas. MET is a key driver of tumor cell growth, motility, invasion, metastasis, and angiogenesis.
About Exelixis
Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis' broad product pipeline includes investigational compounds in Phase II and Phase I clinical development for cancer and renal disease. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies, including GlaxoSmithKline, Bristol-Myers Squibb Company, Genentech, Wyeth Pharmaceuticals and Sankyo. For more information, please visit the company's web site at http://www.exelixis.com.
This press release contains forward-looking statements, including without limitation statements related to the potential efficacy of XL880 in patients with gastric cancer. Words such as "believes," "designed," "may," "potential," "anticipates," "plans," "expects," "intends," "will," "suggests," "goal" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Exelixis' current expectations. Forward-looking statements involve risks and uncertainties. Exelixis' actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the potential failure of product candidates to demonstrate safety and efficacy in clinical testing; the ability to complete and initiate trials at the referenced times; the ability to conduct clinical trials sufficient to achieve a positive completion; the uncertainty of the FDA approval process; and the therapeutic and commercial value of the company's compounds. These and other risk factors are discussed under "Risk Factors" and elsewhere in our quarterly report on Form 10-Q for the quarter ended September 30, 2006 and other filings with the Securities and Exchange Commission. The company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward- looking statements contained herein to reflect any change in the company's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
Exelixis, Inc.
http://www.exelixis.com
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