Exelixis, Inc. EXEL - Exelixis Initiates Phase II Clinical Development Program for XL647 in Patients With Metastatic Non-Small Cell Lung Cancer
Exelixis, Inc. EXEL - Exelixis Initiates Phase II Clinical Development Program for XL647 in Patients With Metastatic Non-Small Cell Lung Cancer
- Study targets previously untreated patients -
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
XL647.
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.
Biotech News
- Study targets previously untreated patients -
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
XL647.
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.
Biotech News
posted by Bill Austin - Exelixis, Inc. EXEL - Exelixis Initiates Phase II Clinical Development Program for XL647 in Patients With Metastatic Non-Small Cell Lung Cancer
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