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Exelixis Initiates Phase II Clinical Development


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Exelixis Initiates Phase II Clinical Development Program for XL647 in Patients With Metastatic Non-Small Cell Lung Cancer

- Study targets previously untreated patients -

SOUTH SAN FRANCISCO, Calif., Aug. 1 /PRNewswire-FirstCall/ -- Exelixis,

Inc. (Nasdaq: EXEL) today announced the initiation of a Phase II trial of

XL647, an orally bioavailable small molecule inhibitor of the HER2, EGF,

VEGF and EphB4 receptor tyrosine kinases (RTKs). Although these individual

RTKs are targets for currently approved therapies, XL647 was designed to

potently inhibit all three targets simultaneously. The trial will be

conducted in patients with advanced (stage IIIB or IV) non-small cell lung

cancer (NSCLC) who have not previously been treated with chemotherapy. In

this proof-of-concept trial, participants must meet at least two of the

following criteria: asian, female, non-smoker or adenocarcinoma.

"We designed XL647 to potently inhibit EGFR and VEGFR, as well as HER2

and EphB4. We believe that simultaneously inhibiting this spectrum of

targets may provide greater efficacy than has been achieved to date by

inhibiting these targets individually," said George A. Scangos, Ph.D.,

president and chief executive officer of Exelixis. "As a single compound

optimized for potency, activity, safety and tolerability, we believe the

safety and tolerability profile of XL647 may be better than those from

combinations of drugs designed to inhibit individual targets."

The multi-center, open-label Phase II study will be conducted in up to

15 clinical sites and will follow a two-stage enrollment strategy. The

primary objectives of the Phase II study are to determine the response rate

of subjects with NSCLC treated with XL647 and to evaluate the safety and

tolerability of XL647. Secondary objectives include assessment of

progression-free survival, duration of response, and overall survival, and

characterization of pharmacokinetic and pharmacodynamic parameters of


As reported in June 2006 at the American Society of Clinical Oncology

(ASCO) annual meeting, XL647 has exhibited favorable safety and

tolerability profiles in a Phase I trial in patients with advanced solid

tumors. The investigators reported that of 40 evaluable patients, one

patient (non-small cell lung cancer [NSCLC]) has had a partial response and

12 others (NSCLC [3], chordoma [2], adenoid cystic carcinoma [2],

adrenocortical carcinoma, colorectal, ovarian, mesothelioma and head and

neck cancer) have had prolonged stable disease (>3.5 months). The first two

patients treated at the 7.0 mg/kg dose experienced dose-limiting toxicities

(DLTs) of grade 3 diarrhea, which resolved upon a reduction in dose to 4.68

mg/kg. One serious adverse event of grade 4 pulmonary embolism was

considered potentially related to study treatment in a patient treated at

the 0.28 mg/kg dose. One patient at the 3.12 mg/kg dose had an asymptomatic

QTc prolongation on electrocardiogram. Expansion of the 4.68 mg/kg cohort

to six patients occurred without further DLTs, and this is considered the

maximum tolerated dose.

About XL647

XL647 is a potent inhibitor of multiple RTKs implicated in driving

tumor cell proliferation and tumor vascularization (blood vessel

formation). XL647 inhibits the EGF, HER2, and VEGF RTKs, each of which is a

target of currently approved cancer therapies. In addition, XL647 inhibits

EphB4, an RTK that is highly expressed in many human tumors and plays a

role in promoting angiogenesis. In a broad array of preclinical tumor

models including breast, lung, colon and prostate cancer, XL647

demonstrated potent inhibition of tumor growth and caused tumor regression.

In cell culture models, XL647 retained significant potency against mutant

EGFRs that cause resistance to current EGFR inhibitors.

About Exelixis

Exelixis, Inc. is a biotechnology company dedicated to the discovery

and development of novel therapeutics that will potentially enhance the

care and lives of patients with cancer and other serious diseases. The

company is leveraging its fully integrated gene-to-drug platform to fuel

the growth of its proprietary drug pipeline. Exelixis' development pipeline

covers cancer and metabolism and is comprised of the following compounds:

XL119 (becatecarin), for which a multinational Phase III clinical trial in

bile duct tumor is ongoing and which has been exclusively licensed to

Helsinn Healthcare S.A.; XL784, which is being advanced in a Phase II trial

as a treatment for renal disease; XL999, an anticancer compound currently

in Phase II clinical trials for a variety of solid tumors and hematologic

malignancies; XL647 an anticancer compound currently in Phase II clinical

trials for advanced non-small cell lung cancer; XL820, XL844 and XL184,

anticancer compounds currently in Phase I clinical trials; and multiple

compounds in preclinical development for diseases including cancer and

various metabolic and cardiovascular disorders. Exelixis has established

broad corporate alliances with major pharmaceutical and biotechnology

companies including GlaxoSmithKline (GSK) and Bristol-Myers Squibb Company.

Pursuant to a product development and commercialization agreement between

Exelixis and GSK, GSK has the option, after completion of clinical

proof-of-concept by Exelixis, to elect to develop a certain number of

compounds in Exelixis' product pipeline, which may include XL784 and the

cancer compounds identified in this press release (other than XL119), thus

potentially triggering milestone payments and royalties from GSK and

co-promotion rights by Exelixis. 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 Exelixis' clinical development

program for XL647 and the therapeutic potential of XL647. Words such as

"believes," "anticipates," "plans," "expects," "intends," "will," "slated,"

"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 of Helsinn Healthcare

S.A. to conduct the Phase III clinical trial of XL119 sufficient to achieve

FDA approval; the ability to complete and initiate trials at the referenced

times; the ability to conduct clinical trials sufficient to achieve a

positive completion; the ability to file INDs at the referenced times; the

ability of Exelixis to advance additional preclinical compounds into

clinical development; 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 March 31, 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.

SOURCE Exelixis, Inc.

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