SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Sep. 30, 2012--
Exelixis, Inc. (NASDAQ:EXEL) today reported preliminary data from an
ongoing phase 1 dose escalation study of cabozantinib in Japan. Hiroshi
Nokihara, M.D., Ph.D., a physician at the National Cancer Center
Hospital in Tokyo, Japan, and an investigator on the trial, presented
the data today in a poster discussion session at the European Society
for Medical Oncology 2012 Annual Meeting (Abstract #1708PD) in Vienna,
Austria.
The primary objective of the phase 1, open label, multiple cohort dose
escalation study is to determine the recommended phase 2 dose of
cabozantinib administered once-daily over a 4-week cycle in Japanese
patients with advanced or metastatic solid tumors. Doses evaluated were
40 mg, 60 mg, or 80 mg of cabozantinib in the capsule configuration.
Secondary objectives are to assess the safety and tolerability of
multiple doses of cabozantinib, plasma pharmacokinetics, and tumor
response.
As of the June 30, 2012 cut-off, 14 patients with a variety of solid
tumors had been enrolled in the study: non-small cell lung cancer
(NSCLC) (5), gastrointestinal stromal tumor (4), colorectal cancer (2),
medullary thyroid cancer (1), thymic cancer (1), and leiomyosarcoma (1).
The median number of prior treatments was 3 (range: 2-6) for all 14
patients, and 4 (range: 2-6) for the NSCLC subgroup. Dose-limiting
toxicity of Grade 3 hypertension was reported in 2 patients, and the
recommended phase 2 dose is 60 mg daily. Pharmacokinetic analyses show
that cabozantinib exhibited dose-linear increases in exposure over the
range of doses evaluated, and a 5- to 6-fold accumulation was observed
on Day 19 following repeated daily dosing. These analyses also show that
cabozantinib exposure in Japanese patients is approximately 2-fold
higher than that observed in non-Japanese patients.
Of the 14 patients, 4 had confirmed partial responses (cPR) as their
best tumor response, 8 had stable disease of at least 12 weeks, and 2
had progressive disease. Eleven of the 14 patients had decreases in
tumor size compared with baseline. The 4 cPRs were observed in the NSCLC
subgroup of 5 patients. All 5 NSCLC patients had tumor regression
ranging from 33% to 41%. All 4 patients with a cPR had mutations or
translocations involving either EGFR, RET, or ALK, while the NSCLC
patient with a best response of stable disease had no mutations in these
genes or in KRAS. Treatment duration for the NSCLC subgroup ranged from
4 to 15+ months. Five patients remained on study as of the June 30, 2012
cut-off.
The most common adverse events (AEs) of grade 3 or higher, regardless of
causality, were: hypertension (3 patients), neutropenia (2), palmar
plantar erythrodyesthesia (1), lipase increased (1), GGT increased (1),
and lymphopenia (1). Five serious AEs have been reported in 3 patients,
including anemia, hematemesis, intestinal obstruction, melena (all
related to cabozantinib), and pleural effusion (unrelated to
cabozantinib).
“The data from this phase 1 study in Japanese patients provide an
initial signal of anti-tumor activity at generally well-tolerated doses
of cabozantinib,” said Michael M. Morrissey, Ph.D., president and chief
executive officer of Exelixis. “We intend to further explore the
potential of cabozantinib in selected patient populations with specific
mutations commonly found in Japanese NSCLC patients.”
About Cabozantinib
Cabozantinib inhibits MET and VEGFR2. Cabozantinib is an investigational
agent that provides coordinated inhibition of metastasis and
angiogenesis to kill tumor cells while blocking their escape pathways.
MET is upregulated in many tumor types, thus facilitating tumor cell
escape by promoting the formation of more aggressive phenotypes,
resulting in metastasis. MET-driven metastasis may be further stimulated
by hypoxic conditions in the tumor environment, which are often
exacerbated by selective VEGF-pathway inhibitors. Exelixis submitted a
new drug application (NDA) for cabozantinib as a treatment for patients
with progressive, unresectable, locally advanced, or metastatic
medullary thyroid cancer to the United States Food and Drug
Administration. The Prescription Drug User Fee Act (PDUFA) action date
for the NDA is November 29, 2012.
About Exelixis
Exelixis, Inc. is a biotechnology company committed to developing small
molecule therapies for the treatment of cancer. Exelixis is focusing its
proprietary resources and development efforts exclusively on
cabozantinib (formerly known as XL184), its most advanced product
candidate, in order to maximize the therapeutic and commercial potential
of this compound. Exelixis has also established a portfolio of other
novel compounds that it believes have the potential to address serious
unmet medical needs, many of which are being advanced by partners as
part of collaborations. For more information, please visit the company's
web site at www.exelixis.com.
Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical, therapeutic and commercial potential of cabozantinib; the
significance of the referenced data; and potential future regulatory
approval of cabozantinib and the timing thereof. Words such as
“objective,” “show,” “signal,” “intend,” “further,” “explore,”
“potential,” and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based
upon Exelixis' current plans, assumptions, beliefs and 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: risks
related to the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; Exelixis’ ability to conduct clinical
trials of cabozantinib sufficient to achieve a positive completion; the
sufficiency of Exelixis’ capital and other resources; the uncertain
timing and level of expenses associated with the development of
cabozantinib; the uncertainty of the FDA approval process; market
competition; and changes in economic and business conditions. These and
other risk factors are discussed under “Risk Factors” and elsewhere in
Exelixis’ quarterly report on Form 10-Q for the quarter ended June 29,
2012, filed with the Securities and Exchange Commission (SEC) on August
2, 2012, and Exelixis’ other filings with the SEC. Exelixis expressly
disclaims any duty, obligation or undertaking to release publicly any
updates or revisions to any forward-looking statements contained herein
to reflect any change in Exelixis’ expectations with regard thereto or
any change in events, conditions or circumstances on which any such
statements are based.
Source: Exelixis, Inc.
Exelixis, Inc.
Charles Butler, 650-837-7277
Vice President,
Investor Relations and Corporate Communications
cbutler@exelixis.com
