– Accepted as a late-breaking oral presentation at the 2018
American Society of Clinical Oncology’s Gastrointestinal Cancers
Symposium (ASCO-GI), January 18-20, 2018 –
– Exelixis to submit supplemental New Drug Application to U.S.
Food and Drug Administration (FDA) in the first quarter of 2018 –
– Cabozantinib previously granted orphan drug designation for the
treatment of hepatocellular carcinoma (HCC) by FDA –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Nov. 21, 2017--
Inc. (NASDAQ:EXEL) today announced that the phase 3 CELESTIAL trial
results have been accepted as a late-breaking presentation at the 2018
ASCO-GI Symposium, which is being held January 18–20, 2018 in San
Francisco. Detailed results from CELESTIAL, the randomized,
double-blind, placebo-controlled study of cabozantinib versus placebo in
patients with advanced HCC who have received prior treatment with
sorafenib, will be presented during Oral Abstract Session B: Cancers of
the Pancreas, Small Bowel, and Hepatobiliary Tract, which begins at 2:15
p.m. PT on Friday, January 19, 2018.
Abstract 207: Cabozantinib (C) versus placebo (P) in patients (pts) with
advanced hepatocellular carcinoma (HCC) who have received prior
sorafenib: results from the randomized phase 3 CELESTIAL trial.
Ghassan K. Abou-Alfa, MD, Memorial Sloan-Kettering Cancer Center, New
On October 16, 2017, Exelixis announced that the CELESTIAL trial met its
primary endpoint of overall survival (OS), with cabozantinib providing a
statistically significant and clinically meaningful improvement in OS
compared with placebo in patients with advanced HCC. The independent
data monitoring committee for the study recommended that the trial be
stopped for efficacy following review of the second planned interim
About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of
cabozantinib in patients with advanced HCC conducted at more than 100
sites globally in 19 countries. The trial was designed to enroll 760
patients with advanced HCC who received prior sorafenib and may have
received up to two prior systemic cancer therapies for HCC and had
adequate liver function. Enrollment of the trial was completed in
September 2017. Patients were randomized 2:1 to receive 60 mg of
cabozantinib once daily or placebo and were stratified based on etiology
of the disease (hepatitis C, hepatitis B or other), geographic region
(Asia versus other regions) and presence of extrahepatic spread and/or
macrovascular invasion (yes or no). No cross-over was allowed between
the study arms.
The primary endpoint for the trial is OS, and secondary endpoints
include objective response rate and progression-free survival.
Exploratory endpoints include patient-reported outcomes, biomarkers and
Based on available clinical trial data from various published trials
conducted in the second-line setting of advanced HCC, the CELESTIAL
trial statistics for the primary endpoint of OS assumed a median OS of
8.2 months for the placebo arm. A total of 621 events provide the study
with 90 percent power to detect a 32 percent increase in median OS (HR =
0.76) at the final analysis. Two interim analyses were planned and
conducted at 50 percent and 75 percent of the planned 621 events.
Liver cancer is the third-leading cause of death worldwide, and
hepatocellular carcinoma (HCC) is the most common form, making up about
three-fourths of the nearly 41,000 cases that will be diagnosed in 2017
in the U.S.1,2 Without treatment, patients with advanced
disease usually survive less than 6 months, and it is estimated that
29,000 people will die due to liver cancer in the U.S.3
Worldwide, nearly 800,000 new cases are diagnosed annually, and the
disease accounts for more than 700,000 deaths each year.4
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced RCC who have received prior anti-angiogenic
therapy. CABOMETYX tablets are also approved in the European Union,
Norway and Iceland for the treatment of advanced RCC in adults who have
received prior vascular endothelial growth factor (VEGF)-targeted
therapy. In 2016, Exelixis granted Ipsen exclusive rights for the
commercialization and further clinical development of cabozantinib
outside of the United States and Japan. In 2017, Exelixis granted
exclusive rights to Takeda Pharmaceutical Company Limited for the
commercialization and further clinical development of cabozantinib for
all future indications in Japan, including RCC.
CABOMETYX is not indicated for the treatment of advanced HCC.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
U.S. Important Safety Information
Severe Hemorrhage occurred with CABOMETYX. In two RCC studies,
Grade ≥3 hemorrhagic events occurred in 2.1% of CABOMETYX patients vs
1.6% with everolimus and in 5.1% of CABOMETYX patients vs 1.4% with
sunitinib. Fatal hemorrhages also occurred in the cabozantinib
clinical program. Do not administer CABOMETYX to patients that
have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas were reported
with CABOMETYX. In two RCC studies, GI perforations occurred in 0.9%
of CABOMETYX patients vs 0.6% with everolimus and in 2.6% of CABOMETYX
patients vs 0% with sunitinib. Fatal perforations occurred in the
cabozantinib clinical program. Fistulas were reported in 1.2%
(including 0.6% anal fistula) of CABOMETYX patients vs 0% with
everolimus. Monitor patients for symptoms of perforations and
fistulas. Discontinue CABOMETYX in patients who experience a GI
perforation or a fistula that cannot be appropriately managed.
Thrombotic Events increased with CABOMETYX. In two RCC studies,
arterial thromboembolism events were reported in 0.9% of CABOMETYX
patients vs 0.3% with everolimus and 1.3% of CABOMETYX patients vs
5.6% with sunitinib. Pulmonary embolism events were reported in 3.9%
of CABOMETYX patients vs 0.3% with everolimus and 9% of CABOMETYX
patients vs 0% with sunitinib. Venous thromboembolism occurred in 7.3%
of CABOMETYX patients vs 2.5% with everolimus. Fatal thrombotic events
occurred in the cabozantinib clinical program. Discontinue CABOMETYX
in patients who develop an acute myocardial infarction, cerebral
infarction, or other serious arterial thromboembolic complication.
Hypertension and Hypertensive Crisis occurred with CABOMETYX.
In two RCC studies, treatment-emergent hypertension increased with
CABOMETYX. Hypertension was reported in 37% (15% Grade ≥3) of
CABOMETYX patients vs 7.1% (3.1% Grade ≥3) with everolimus and in 67%
(28% Grade ≥3) of CABOMETYX patients vs 44% (21% Grade ≥3) with
sunitinib. Monitor blood pressure prior to initiation and regularly
during CABOMETYX treatment. Withhold CABOMETYX for hypertension that
is not adequately controlled with medical management; when controlled,
resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for
hypertensive crisis or severe hypertension that cannot be controlled
with antihypertensive therapy or medical management.
Diarrhea occurred with CABOMETYX. In two RCC trials, diarrhea
occurred in 74% (11% Grade 3) of CABOMETYX patients vs 28% (2% Grade
3) with everolimus and in 73% (10% Grade 3) of CABOMETYX patients vs
54% (11% Grade 3) with sunitinib. Withhold CABOMETYX in patients who
develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot
be managed with standard antidiarrheal treatments until improvement to
Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurred with
CABOMETYX. In two RCC trials, PPES occurred in 42% (8.2% Grade 3) of
CABOMETYX patients vs 6% (<1% Grade 3) with everolimus and in 42%
(7.7% Grade 3) of CABOMETYX patients vs 33% (4.2% Grade 3) with
sunitinib. Withhold CABOMETYX in patients who develop intolerable
Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume
CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a
syndrome of subcortical vasogenic edema diagnosed by characteristic
finding on MRI, occurred in the cabozantinib clinical program.
Evaluate for RPLS in patients presenting with seizures, headache,
visual disturbances, confusion, or altered mental function.
Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise
pregnant women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during CABOMETYX
treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse
reactions are: diarrhea, fatigue, nausea, decreased appetite,
hypertension, PPES, weight decreased, vomiting, dysgeusia, and
Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce
the dosage of CABOMETYX if concomitant use with strong CYP3A4
inhibitors cannot be avoided. Increase the dosage of CABOMETYX if
concomitant use with strong CYP3A4 inducers cannot be avoided.
Lactation: Advise women not to breastfeed while taking
CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic
impairment, reduce the CABOMETYX dosage. CABOMETYX is not
recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information https://cabometyx.com/downloads/cabometyxuspi.pdf.
Founded in 1994, Exelixis, Inc. (NASDAQ:EXEL) is a commercially
successful, oncology-focused biotechnology company that strives to
accelerate the discovery, development and commercialization of new
medicines for difficult-to-treat cancers. Following early work in model
genetic systems, we established a broad drug discovery and development
platform that has served as the foundation for our continued efforts to
bring new cancer therapies to patients in need. We discovered our lead
compounds, cabozantinib and cobimetinib, and advanced them into clinical
development before entering into partnerships with leading
biopharmaceutical companies in our efforts to bring them to patients
globally. We are steadfast in our commitment to prudently reinvest in
our business to maximize the potential of our pipeline. We intend to
supplement our existing therapeutic assets with targeted business
development activities and internal drug discovery – all to deliver the
next generation of Exelixis medicines and help patients recover stronger
and live longer. Exelixis recently earned a spot on Deloitte’s
Technology Fast 500 list, a yearly award program honoring the 500
fastest-growing companies over the past four years. For more information
about Exelixis, please visit www.exelixis.com
or follow @ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plan to submit an
supplemental New Drug Application to the FDA in the first quarter of
2018 for cabozantinib as a treatment for patients with advanced HCC;
Exelixis’ plan to present the detailed results from CELESTIAL at the
2018 ASCO-GI; Exelixis’ commitment to reinvesting in its business to
maximize the potential of its pipeline, including supplementing its
existing therapeutic assets through targeted business development
activities and internal drug discovery; and Exelixis’ mission to deliver
the next generation of Exelixis medicines and help patients recover
stronger and live longer. Words such as “to be,” “will,” “commitment,”
“potential,” “plan,” “mission,” 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.
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: risks and
uncertainties related to regulatory review and approval processes and
Exelixis’ compliance with applicable legal and regulatory requirements;
the availability of data at the referenced time; the level of costs
associated with Exelixis’ commercialization, research and development
and other activities; competition in the area of business development
activities and the inherent uncertainty of the drug discovery process;
Exelixis’ ability and the ability of its collaborators to conduct
clinical trials of cabozantinib and cobimetinib both alone and in
combination with other therapies sufficient to achieve a positive
completion; risks related to the potential failure of cabozantinib and
cobimetinib both alone and in combination with other therapies, to
demonstrate safety and efficacy in clinical testing; Exelixis’
dependence on its relationships with its cabozantinib collaboration
partners, including, the level of their investment in the resources
necessary to successfully commercialize cabozantinib in the territories
where it is approved; Exelixis’ dependence on its relationship with
Genentech/Roche with respect to cobimetinib and Exelixis’ ability to
maintain its rights under the collaboration; market acceptance of
CABOMETYX, COMETRIQ, and COTELLIC and the availability of coverage and
reimbursement for these products; Exelixis’ dependence on third-party
vendors for the development, manufacture and supply of its products;
Exelixis’ ability to protect the company’s intellectual property rights;
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 November 1, 2017, and in Exelixis’ future 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 based.
Hepatocellular Carcinoma – United States, 2001-2006. Morbidity and
Mortality Weekly Report. Centers for Disease Control and Prevention.
Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5917a3.htm.
Accessed November 2017.
American Cancer Society: Cancer Facts and Figures 2017. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf.
Accessed November 2017.
Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular
carcinoma? Annals of Medicine and Surgery. 2014. (3):71-76.
Estimated cancer incidence, mortality and prevalence worldwide.
International Agency for Research on Cancer, GLOBOCAN 2012. Available
Accessed November 2017.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171121006072/en/
Source: Exelixis, Inc.
EVP, Public Affairs and Investor Relations
Claire McConnaughey, 650-837-7052
Manager, Public Affairs