PRAGUE, Czech Republic, Nov. 9 /PRNewswire-FirstCall/ -- Exelixis, Inc. announces that updated Phase I data from an ongoing trial of XL880 in patients with advanced solid tumors were reported today. Results demonstrate that XL880 is generally well tolerated at doses up to the maximum tolerated dose (MTD) of 3.6 mg/kg and shows anti-tumor activity. Dr. Patricia LoRusso of the Karmanos Cancer Center in Detroit and an investigator in the study presented the data in a poster (Abstract #404) at the 18th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, which is being held November 7-10 in Prague, Czech Republic. A Phase II trial of XL880 in patients with papillary renal cell carcinoma was initiated in June 2006 and is ongoing.
As of October 6, 2006, 40 patients had been enrolled in the Phase I trial and were evaluable for safety; and 29 of which were also evaluable for pharmacokinetic analyses. 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]).
With respect to biomarkers for XL880 activity, analyses of melanoma, breast and medullary thyroid tumor samples indicate that XL880 decreases the phosphorylation status of Met, RON, ERK, and AKT, decreases Ki67, a marker for tumor cell proliferation, and increases apoptosis of tumor and endothelial cells. This effect was not observed in samples of normal tissue obtained at the same time points.
“XL880 is the first oral small molecule Met inhibitor to enter clinical development, and the results of this Phase I trial to date appear to support the hypothesis that Met is an important target for cancer therapy,” said Gisela M. Schwab, M.D., senior vice president and chief medical officer of Exelixis. “The partial responses observed in three patients with papillary renal cell carcinoma in this study provide a compelling rationale for our ongoing Phase II trial of XL880 in this indication. The additional tumor response, disease stabilization and biomarker activity indicate that XL880 is able to inhibit Met and Ron and their downstream effectors ERK and AKT, and suggest that the compound may have utility in treating a variety of solid tumors.”
Two serious adverse events in the maximum administered dose (MAD) cohort of 4.5 mg/kg that were reported as possibly and probably related to study drug included a grade 3 tumor hemorrhage and a grade 3 hand/foot syndrome. One serious event of confusion, altered speech or “expressive language disorder” was reported for one patient in the MTD cohort at the 3.6 mg/kg dose. The event was grade 2, fully reversible, and the patient continues on study with minimal response at 2.4 mg/kg and no recurrence of symptoms. Grade 2 or greater adverse events considered possibly or probably related to XL880 treatment in at least two patients included fatigue (grade 2, two patients) and hypertension (grade 2, two patients). Hypertension is a dose-related side effect.
Additional Information
Exelixis’ clinical investigators will discuss clinical data on XL999, XL880, XL820 and XL184 in conjunction with data presentations at the conference. The discussion will take place in Prague at 6:00 p.m. (local time) / 12:00 p.m. (ET) / 9:00 a.m. (PT) on Thursday, November 9, 2006. The discussion will be webcast and archived and may be accessed in the Event Calendar page under Investors at www.exelixis.com . Additionally, the XL880 poster presented at the conference may be accessed in the Pipeline page at www.exelixis.com upon the conclusion of the conference.
About the Trial
This Phase I, nonrandomized, open-label, dose-finding trial is being conducted in patients aged 18 years or older with histologically confirmed advanced solid malignancy that is metastatic or unresectable and for which alternative therapies do not exist or are no longer effective. Patients with advanced solid malignancies were enrolled in successive cohorts to receive XL880 orally as a single dose on day 1, followed by 5 continuous daily doses starting on day 4. Patients then continued to receive dosing for 5 continuous days followed by a break with cycles repeated every 14 days. Patients were allowed to receive continued therapy with XL880 in the absence of unacceptable toxicity until evidence of disease progression. The primary objective of the Phase I dose escalation trial was to establish a MTD and to assess safety and tolerability of oral administration of XL880. Secondary objectives included PK analyses and tumor response.
About XL880
XL880 is an orally available 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 (ligand for MET) and vascular endothelial growth factor RTK families, although platelet-derived growth factor receptor (PDGFR), c-KIT, FLT3 and Tie-2 are also inhibited. Activation or overexpression of MET has been documented as a negative prognostic indicator in patients with various carcinomas, and in patients with multiple myeloma, glioma and other solid tumors. Activation of MET by mutation is the causative factor in an inherited kidney cancer syndrome, hereditary papillary renal cell carcinoma. Mutational 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. XL880 is the first orally bioavailable small molecule MET inhibitor to enter the clinic.
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 III (XL119, exclusively out-licensed to Helsinn Healthcare S.A.), 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 www.exelixis.com .
This press release contains forward-looking statements. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “slated,” “goal,” “promising” 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, which could prevent or significantly delay regulatory approval; 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.
CONTACT: investors, Charles Butler, Director, Corporate Communications,+1-650-837-7277, or cbutler@exelixis.com, or media, Soleil MaxwellHarrison, Senior Manager, Corporate Communications, +1-650-837-7012, orsharrison@exelixis.com, both of Exelixis, Inc.
Web site: http://www.exelixis.com//
