-- Cabozantinib, as well as the combination of cabozantinib and
erlotinib, significantly improved progression-free survival and overall
survival compared with erlotinib alone
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 31, 2015--
Exelixis, Inc. (NASDAQ:EXEL) today announced positive results from a
phase 2 clinical study evaluating cabozantinib as a treatment for EGFR
wild-type non-small cell lung cancer (NSCLC). The trial, Study E1512, is
a randomized phase 2 trial by the ECOG-ACRIN Cancer Research Group of
cabozantinib and erlotinib, alone or in combination, as second- or
third-line therapy in patients with metastatic EGFR wild-type NSCLC.
Exelixis previously announced positive top-line results from this trial
in November 2014. Data from the trial will be presented today during an
oral presentation (Abstract #8003) at the 2015 Annual Meeting of the
American Society of Clinical Oncology (ASCO), which is being held this
week in Chicago, Illinois. Study chair Joel Neal, M.D., Ph.D., of
ECOG-ACRIN's Thoracic Cancer Committee and an Assistant Professor of
Medicine (Oncology) at Stanford University/Stanford Cancer Institute
will present the results.
Study E1512 met its primary endpoint, demonstrating significant
increases in progression-free survival (PFS) for cabozantinib and the
combination of cabozantinib plus erlotinib when individually compared to
the erlotinib arm. The median PFS for the combination of cabozantinib
and erlotinib was 4.7 months versus 1.9 months for erlotinib alone, a
more than two-fold increase that corresponds to a 65% reduction in the
risk of disease worsening (hazard ratio [HR]=0.35, 80% CI 0.23-0.52,
p=0.0005). The median PFS for cabozantinib monotherapy was 4.2 months
versus 1.9 months for erlotinib alone, a more than doubling that
corresponds to a 62% reduction in the risk of disease worsening
(HR=0.38, 80% CI 0.27-0.55, p=0.0004).
Overall survival was a secondary endpoint of the trial. Median OS was
13.3 months for the combination of cabozantinib and erlotinib, and 9.2
months for cabozantinib alone, as compared to 4.1 months for erlotinib
alone. These results correspond to a 56% reduction in the risk of death
(HR=0.44, p=0.004) for the combination of cabozantinib plus erlotinib,
and a 41% reduction in the risk of death (HR=0.59, p=0.03) for the
cabozantinib monotherapy arm, respectively, when individually compared
to the erlotinib arm. Objective response rate, another secondary
endpoint, was 8% for the combination arm (2 partial responses [PR]), 14%
(4 PRs) for the cabozantinib monotherapy arm, and 3% (1 PR) for the
erlotinib arm. Stable disease as a best response was observed in 47% in
the combination arm and 42% in the cabozantinib monotherapy arm,
compared with 17% in the erlotinib arm.
118 patients were evaluable for safety. The most common
treatment-related adverse events (AEs), grade 3 or higher, for the
combination arm (n=39) were: diarrhea (27%), fatigue (15%), and syncope
(8%). For the cabozantinib monotherapy arm, the most common AEs, grade 3
or higher, were: hypertension (26%), fatigue (15%), mucositis (10%) and
thromboembolic events (8%). The most common AEs, grade 3 or higher, for
the erlotinib arm were fatigue (12%) and diarrhea (8%). Overall, the
rate of grade 3 or higher worst grade adverse events was 72% in the
combination arm and 67% in the cabozantinib monotherapy arm, compared
with the erlotinib arm (35%).
“Despite the availability of new therapies, lung cancer continues to
pose significant clinical challenges,” said ECOG-ACRIN group co-chair
Robert L. Comis, M.D. “The magnitudes of improvement in progression-free
survival and overall survival delivered by the combination and single
agent cabozantinib arms in this randomized phase 2 trial are
encouraging, and they provide a strong rationale for further evaluation
of cabozantinib in non-small cell lung cancer.”
Commenting on the results, Michael M. Morrissey, Ph.D., Exelixis’
president and chief executive officer, said: “The results from Study
E1512 demonstrate cabozantinib’s ability to extend progression-free
survival and overall survival in a randomized phase 2 trial in
comparison with erlotinib, an active comparator. The data also speak to
cabozantinib’s potential as a component of combination therapy in
non-small cell lung cancer. Exelixis is committed to working with our
partners at ECOG-ACRIN and the National Cancer Institute to evaluate
that potential, and we look forward to discussing possible next steps,
including combination trials with immunotherapies, as well as potential
pivotal studies in late-line disease.”
Study E1512 enrolled 125 patients with metastatic EGFR wild-type NSCLC
who had received at one or two prior chemotherapy regimens; of these,
113 patients were evaluable for efficacy and 118 patients were evaluable
for safety. Patients were randomized 1:1:1 to receive erlotinib (150 mg
daily), cabozantinib (60 mg daily), or the combination of erlotinib plus
cabozantinib (150 mg plus 40 mg daily). Median follow up was 12.6
months. Baseline characteristics were generally well balanced between
the treatment arms with the exception of a history of treated brain
metastases (combination arm 25%, cabozantinib monotherapy arm 33%, and
erlotinib monotherapy arm 8%) and a history of mediastinal metastases
(combination arm 50%, cabozantinib monotherapy arm 56%, and erlotinib
monotherapy arm 30%). The primary objective of the trial was to compare
the PFS of patients on the cabozantinib and combination arms versus that
of the erlotinib arm. Each comparison had 91% power to detect a PFS
hazard ratio (HR) of 0.5 with a 1-sided 0.10-level test stratified on
prior number of therapies and ECOG performance status.
The trial is sponsored by the U.S. National Cancer Institute (NCI) under
a Cooperative Research and Development Agreement between the NCI’s
Cancer Therapy Evaluation Program (CTEP) and Exelixis. The study was
designed and is being conducted by the ECOG-ACRIN Cancer Research Group
as part of Exelixis’ collaboration with the NCI.
Cabozantinib inhibits the activity of tyrosine kinases including MET,
VEGFRs and RET. These receptor tyrosine kinases are involved in both
normal cellular function and in pathologic processes such as
oncogenesis, metastasis, tumor angiogenesis, and maintenance of the
COMETRIQ® (cabozantinib) is currently approved by the U.S. Food and Drug
Administration for the treatment of progressive, metastatic medullary
thyroid cancer (MTC).
The European Commission granted COMETRIQ conditional approval for the
treatment of adult patients with progressive, unresectable locally
advanced or metastatic MTC. Similar to another drug approved in this
setting, the approved indication states that for patients in whom
Rearranged during Transfection (RET) mutation status is not known or is
negative, a possible lower benefit should be taken into account before
individual treatment decisions.
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed
Avoid administration of COMETRIQ with agents that are strong CYP3A4
inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or
severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS,
Please refer to the full European Summary of Product Characteristics for
full European Union prescribing information, including contraindication,
special warnings and precautions for use at www.sobi.com
The ECOG-ACRIN Cancer Research Group is a membership-based scientific
organization that designs and conducts cancer research involving adults
who have or are at risk of developing cancer. ECOG-ACRIN comprises
nearly 1100 member institutions and 12,000 research professionals in the
United States and around the world. For more information, please visit
the organization’s website at www.ecog-acrin.org.
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of multiple
receptor tyrosine kinases. Another Exelixis-discovered compound,
cobimetinib, a selective inhibitor of MEK, is being evaluated by Roche
and Genentech, Inc. (a member of the Roche Group) in a broad development
program under a collaboration with Exelixis. For more information,
please visit the company's web site at www.exelixis.com.
This press release contains forward-looking statements, including,
without limitation, statements related to: future data presentations of
for the phase 2 clinical study evaluating cabozantinib as a treatment
for EGFR wild-type NSCLC; potential future evaluation of cabozantinib in
NSCLC; the continued development and clinical, therapeutic and
commercial potential of, and opportunities for, cabozantinib as a
component of combination therapy in NSCLC; and Exelixis’ commitment to
working with its partners to evaluate such potential. Words such as
“continues,” “will,” “encouraging,” “further,” “potential,” “committed,”
“look forward,” “next steps,” or other similar expressions, identify
forward-looking statements, but the absence of these words does not
necessarily mean that a statement is not forward-looking. In addition,
any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements. These forward-looking statements are based upon Exelixis’
current plans, assumptions, beliefs, expectations, estimates and
projections. Forward-looking statements involve risks and uncertainties.
Exelixis’ actual results and the timing of events could differ
materially from those anticipated in the forward-looking statements as a
result of these risks and uncertainties, which include, without
limitation: the availability of data at the expected times; risks
related to the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; the clinical, therapeutic and
commercial value of cabozantinib; the uncertain timing and level of
expenses associated with the development of cabozantinib; Exelixis’
ability and the ability of its partners to conduct clinical trials of
cabozantinib sufficient to achieve a positive completion; market
competition; changes in economic and business conditions; and other
factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on April 30, 2015 and in Exelixis’ other filings with
the SEC. The forward-looking statements made in this press release speak
only as of the date of this press release. 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
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
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Source: Exelixis, Inc.
Investor Relations and Corporate
For Exelixis, Inc.