– Thyroid cancer is the most rapidly increasing cancer in the U.S.,
with incidence tripling over the past 30 years –
ALAMEDA, Calif.--(BUSINESS WIRE)--Oct. 8, 2018--
Inc. (Nasdaq: EXEL) today announced the initiation of a phase 3
pivotal trial (COSMIC-311) of single-agent cabozantinib in patients with
radioiodine-refractory differentiated thyroid cancer (DTC) who have
progressed after up to two prior vascular endothelial growth factor
receptor (VEGFR)-targeted therapies. The co-primary endpoints for the
trial are progression-free survival and objective response rate.
“Cabozantinib has demonstrated encouraging clinical activity in patients
with radioiodine-refractory differentiated thyroid cancer in phase 1 and
2 studies, suggesting it may be a promising treatment option for
patients who have progressed after prior VEGFR-targeting therapy,” said
Gisela Schwab, M.D., President, Product Development and Medical Affairs
and Chief Medical Officer, Exelixis. “We look forward to enrolling
patients in this global trial to learn more about the potential of
cabozantinib for this intractable form of thyroid cancer.”
COSMIC-311 is a multicenter, randomized, double-blind,
placebo-controlled phase 3 pivotal trial that aims to enroll
approximately 300 patients at approximately 150 sites globally. Patients
will be randomized in a 2:1 ratio to receive either cabozantinib 60 mg
or placebo once daily.
“With the incidence of thyroid cancer increasing more rapidly than any
other type of cancer in the U.S., and limited options available to
patients whose disease has progressed following anti-VEGFR therapy,
there is an urgent need for new treatments,” said Marcia
Brose, M.D., Ph.D., Associate Professor of Otorhinolaryngology: Head and
Neck Surgery and Director of the Center for Rare Cancers and
Personalized Therapy at the Abramson Cancer Center of the University of
Pennsylvania, and principal investigator of the trial. “Given the
positive results from earlier stage trials, we are eager to learn more
from this phase 3 study about cabozantinib’s potential benefit in this
More information about this trial is available at ClinicalTrials.gov.
About Differentiated Thyroid Carcinoma
Thyroid cancer is commonly diagnosed at a younger age than most other
adult cancers and is the most rapidly increasing cancer in the U.S.,
tripling in incidence in the past three decades.1
Approximately 54,000 new cases of thyroid cancer will be diagnosed in
the U.S. in 2018.1 Nearly three out of four of these cases
will be in women.1 Cancerous thyroid tumors include
differentiated, medullary and anaplastic forms.1
Differentiated thyroid tumors, which make up about 90 percent of all
thyroid cancers, are typically treated with surgery followed by ablation
of the remaining thyroid with radioiodine.2 Approximately 5
to 15 percent of differentiated thyroid tumors are resistant to
radioiodine treatment.3 For these patients, life expectancy
is only three to six years from the time metastatic lesions are detected.4,5,6
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of
patients with advanced RCC. CABOMETYX tablets are also approved in: the
European Union, Norway, Iceland, Australia, Switzerland and South Korea
for the treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy; in the European Union for previously untreated
intermediate- or poor-risk advanced RCC; and in Canada for adult
patients with advanced RCC who have received prior VEGF targeted
therapy. In March 2017, the FDA granted orphan drug designation to
cabozantinib for the treatment of advanced HCC. In May 2018, the FDA
accepted Exelixis’ supplemental New Drug Application for CABOMETYX as a
treatment for patients with previously treated HCC and assigned it a
Prescription Drug User Fee Act action date of January 14, 2019. On March
28, 2018, Ipsen announced that the European Medicines Agency validated
its application for a new indication for cabozantinib as a treatment for
previously treated advanced HCC in the European Union; on September 20,
2018 the CHMP provided a positive opinion for CABOMETYX as a monotherapy
for the treatment of HCC in adults who have been previously treated with
sorafenib. 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.
CABOMETYX is not indicated for radioiodine-refractory DTC.
Please see Important Safety Information below and full U.S. prescribing
information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
U.S. Important Safety Information
Hemorrhage: Severe and fatal hemorrhages have occurred with
CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic
events was 3% in CABOMETYX-treated patients. Do not administer
CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC
studies, fistulas were reported in 1% of CABOMETYX-treated patients.
Fatal perforations occurred in patients treated with CABOMETYX. In RCC
studies, gastrointestinal (GI) perforations were reported in 1% of
CABOMETYX-treated patients. Monitor patients for symptoms of fistulas
and perforations, including abscess and sepsis. Discontinue CABOMETYX
in patients who experience a fistula which cannot be appropriately
managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased
incidence of thrombotic events. In RCC studies, venous thromboembolism
occurred in 9% (including 5% pulmonary embolism) and arterial
thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal
thrombotic events occurred in the cabozantinib clinical program.
Discontinue CABOMETYX in patients who develop an acute myocardial
infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment
results in an increased incidence of treatment-emergent hypertension,
including hypertensive crisis. In RCC studies, hypertension was
reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. 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 severe hypertension that
cannot be controlled with anti-hypertensive therapy. Discontinue
CABOMETYX if there is evidence of hypertensive crisis or severe
hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients
treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients
treated with CABOMETYX. 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 (PPE): In RCC studies,
palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients
treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated
with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable
Grade 2 PPE or Grade 3 PPE 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. Perform
an evaluation for RPLS in any patient 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, PPE, weight decreased, vomiting, dysgeusia, and
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4
inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4
inducers cannot be avoided, increase the CABOMETYX dosage.
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 three
commercially available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib) and COTELLIC® (cobimetinib), and have entered into
partnerships with leading pharmaceutical companies to bring these
important medicines to patients worldwide. Supported by revenues from
our marketed products and collaborations, we are committed to prudently
reinvesting in our business to maximize the potential of our pipeline.
We are supplementing 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. In July 2018, Exelixis was added to
the Standard & Poor’s (S&P) MidCap 400 index, which measures the
performance of profitable mid-sized companies. For more information
about Exelixis, please visit www.exelixis.com,
on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the potential of cabozantinib
as a treatment option for patients with radioiodine-refractory
differentiated thyroid cancer who have progressed after prior
VEGFR-targeting therapy; and Exelixis’ plans to reinvest in its business
to maximize the potential of the company’s pipeline, including through
targeted business development activities and internal drug discovery.
Any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements and 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 potential failure of
cabozantinib to demonstrate safety and/or efficacy in COSMIC-311;
uncertainties inherent in the product development process, including
evolving regulatory requirements, slower than anticipated patient
enrollment or inability to identify a sufficient number of clinical
trial sites; the costs of conducting clinical trials, including
Exelixis’ dependence on third-party vendors for the development,
manufacture and supply of cabozantinib; Exelixis’ ability to protect its
intellectual property rights; market competition; changes in economic
and business conditions; and other factors affecting Exelixis and its
development programs discussed under the caption “Risk Factors” in
Exelixis’ Quarterly Report on Form 10-Q filed with the Securities and
Exchange Commission (SEC) on August 1, 2018, and in Exelixis’ future
filings with the SEC. All forward-looking statements in this press
release are based on information available to Exelixis as of the date of
this press release, and Exelixis undertakes no obligation to update or
revise any forward-looking statements contained herein.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
1 American Cancer Society. Key Statistics for Thyroid Cancer. https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html.
Accessed October 2018.
2 Cooper DS, et al. 2009. Revised American Thyroid
Association management guidelines for patients with thyroid nodules and
differentiated thyroid cancer: the American Thyroid Association (ATA)
Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid
Cancer. Thyroid. 19:1167–1214.
3 Worden F. 2014. Treatment strategies for radioactive
iodine-refractory differentiated thyroid cancer. Ther Adv Med Oncol.
4 Xing M, Haugen BR, Schlumberger M. 2013. Progress in
molecular-based management of differentiated thyroid cancer. Lancet.
5 Pacini F, et al. 2012. Radioactive iodine-refractory
differentiated thyroid cancer: unmet needs and future directions. Expert
Rev Endocrinol Metab. 7:541–554.
6 Durante C, et al. 2006. Long-term outcome of 444 patients
with distant metastases from papillary and follicular thyroid carcinoma:
benefits and limits of radioiodine therapy. J Clin Endocrinol Metab.
View source version on businesswire.com: https://www.businesswire.com/news/home/20181008005093/en/
Source: Exelixis, Inc.
EVP, Public Affairs and
Lindsay Treadway, 650-837-7522
Director, Public Affairs and Advocacy Relations