-Phase 3 Pivotal Trial of Cabozantinib in Metastatic
Castration-Resistant Prostate Cancer-
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Sep. 26, 2013--
Exelixis, Inc. (NASDAQ:EXEL) today announced that the enrollment target
of 960 patients has been reached for COMET-1, the company’s phase 3
pivotal trial of cabozantinib in patients with metastatic
castration-resistant prostate cancer (mCRPC). The primary endpoint of
COMET-1 is overall survival, and Exelixis continues to expect top-line
data from COMET-1 and a second pivotal trial in mCRPC, COMET-2, in 2014.
COMET-1 is a randomized, double-blind, placebo-controlled trial designed
to enroll 960 patients with mCRPC who have previously been treated with
docetaxel, abiraterone acetate and/or enzalutamide. All patients in the
trial have bone metastases and there is no limit to the number or type
of prior treatments. Patients are randomized 2:1 to receive cabozantinib
(60 mg daily) or prednisone (5 mg twice daily). The trial is
event-driven and has 90% power to detect a 25% reduction in the risk of
death (HR = 0.75) at the time of final analysis, which requires 578
events. A single interim analysis after 387 events is also planned and
will assess if the trial achieved its primary endpoint; it will not
include a futility analysis. The secondary endpoint of the trial is bone
scan response as assessed by an independent radiology facility (IRF).
“Reaching the COMET-1 enrollment target is a significant milestone for
the cabozantinib clinical development program,” said Michael M.
Morrissey, Ph.D., president and chief executive officer of Exelixis.
“2014 will be an important year for Exelixis as we anticipate top-line
data from four pivotal trials of compounds discovered and developed by
the company: along with expected data from both COMET trials, we
anticipate overall survival data from EXAM, the phase 3 pivotal trial of
cabozantinib that served as the basis for its approval to treat
progressive, metastatic medullary thyroid cancer. In addition, our
partner Genentech, a member of the Roche Group, has guided that it
expects data from the pivotal trial of cobimetinib (GDC-0973/XL518), an
Exelixis-discovered compound, in combination with vemurafenib as a
potential treatment for B-RAF V600 mutation positive, locally advanced
or metastatic melanoma.”
COMET-1 is one of two ongoing company-sponsored pivotal trials of
cabozantinib in mCRPC. The second trial, COMET-2, is a randomized,
double-blind, placebo-controlled phase 3 trial evaluating cabozantinib’s
ability to reduce pain associated with bone metastases. COMET-2
continues to enroll patients, and more information on the trial can be
found at www.cometclinicaltrials.com
Recently initiated phase 3 pivotal trials of cabozantinib in metastatic
renal cell carcinoma and advanced hepatocellular carcinoma are also
actively recruiting patients.
Cabozantinib inhibits the activity of tyrosine kinases including RET,
MET and VEGFR2. 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
tumor microenvironment. COMETRIQ® (cabozantinib) is currently approved
by the U.S. Food and Drug Administration for the treatment of
progressive, metastatic medullary thyroid cancer.
Cobimetinib (GDC-0973/XL518) is a potent, highly selective inhibitor of
MEK, a serine/threonine kinase that is a component of the
RAS/RAF/MEK/ERK pathway. This pathway mediates signaling downstream of
growth factor receptors, and is prominently activated in a wide variety
of human tumors. In preclinical studies, oral dosing of cobimetinib
results in potent and sustained inhibition of MEK in RAS or B-RAF mutant
tumor models, and results in significant tumor regression at
well-tolerated doses. Cobimetinib was designed to have low penetration
into the brain with the aim of minimizing the potential for the CNS side
effects reported with previous MEK inhibitors.
Cobimetinib is being developed by Genentech/Roche under a collaboration
agreement with Exelixis. As part of the agreement, Exelixis has the
option to co-promote in the United States and will be entitled to
receive a share in the profits in the United States. Exelixis will
receive royalties on any sales of the product that may be commercialized
outside the United States.
COMETRIQ® Important Safety Information, including Boxed Warning
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 (PPE) Syndrome 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
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.
Drug Interactions – COMETRIQ is a CYP3A4 substrate. Co-administration of
strong CYP3A4 inhibitors can increase cabozantinib exposure. Chronic
co-administration of strong CYP3A4 inducers can reduce cabozantinib
For full prescribing information, including Boxed Warning, please visit www.COMETRIQ.com.
Exelixis 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 COMETRIQ®
(cabozantinib). 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.
This press release contains forward-looking statements, including,
without limitation, statements related to: the importance of, and
designs, plans and goals for, the COMET-1 and COMET-2 trials, and the
timing (including for the readout of top-line data) and potential
success thereof; the belief that reaching the COMET-1 enrollment target
is a significant milestone for the cabozantinib clinical development
program; the belief that 2014 will be an important year for Exelixis;
anticipated top-line data from four pivotal trials of compounds
discovered and developed by Exelixis; recruitment of patients in the
recently initiated phase 3 pivotal trials of cabozantinib in metastatic
renal cell carcinoma and advanced hepatocellular carcinoma; and the
continued development and clinical, therapeutic and commercial potential
of, and opportunities for, cabozantinib and cobimetinib
(GDC-0973/XL518). Words such as “continues,” “expect,” “designed,”
“planned,” “will,” “endpoint,” “significant,” “milestone,” “important,”
“anticipate,” “potential,” “actively,” “recruiting,” “believe,” 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: the availability of data at the
expected times; risks related to the potential failure of cabozantinib
or cobimetinib (GDC-0973/XL518) to demonstrate safety and efficacy in
clinical testing; the uncertain timing and level of expenses associated
with the development of cabozantinib; Exelixis' ability to conduct
clinical trials of cabozantinib sufficient to achieve a positive
completion; Exelixis' dependence on its relationship with
Genentech/Roche for the development of cobimetinib (GDC-0973/XL518) and
Exelixis’ ability to maintain its rights under the collaboration; the
uncertainty of regulatory approval processes; the sufficiency of
Exelixis' capital and other resources; 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 three months ended June 28, 2013, filed with
the Securities and Exchange Commission (SEC) on August 6, 2013, 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
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
Source: Exelixis, Inc.
Charles Butler, 650-837-7277