– 54 percent objective response rate and 43 percent stable disease
observed among 35 evaluable patients –
– Exelixis plans to initiate a pivotal phase 3 trial later this
– Results to be presented during an oral session on February 16 at
the 2018 Multidisciplinary Head and Neck Cancers Symposium –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Exelixis,
Inc. (NASDAQ:EXEL) today announced results from a phase 2
investigator-sponsored trial (IST) of cabozantinib for the first-line
treatment of metastatic radioiodine (RAI)-refractory differentiated
thyroid carcinoma (DTC). The results were the subject of a news briefing
that took place earlier today and will be presented during an oral
session on February 16 starting at 1:30 p.m. MT at the 2018
Multidisciplinary Head and Neck Cancers Symposium, which is being held
in Scottsdale, Arizona, February 15–17, 2018.
Patients with metastatic, RAI-refractory DTC were enrolled in this
single-arm, open-label trial, and were administered oral cabozantinib 60
mg once daily. The primary endpoint of the trial is objective response
rate. Among the 35 patients who were evaluable for response, partial
response was achieved by 54 percent of patients (n=19), and stable
disease was reported in 43 percent of patients (n=15) per RECIST 1.1.
All but one evaluated patient experienced a decrease in tumor target
lesions. Secondary endpoints of the trial include progression-free
survival (PFS), time to progression (TTP), duration of response (DOR)
and clinical benefit rate (CBR) defined as the number of patients
achieving an objective response or stable disease for at least 6 months.
The CBR at six months was 80 percent (n=28). With a median follow up for
the study of 35 weeks the median PFS has not been reached. The median
TTP among those patients who progressed was 35 weeks.
“While many patients with differentiated thyroid cancer can be treated
successfully with radioiodine, there are very few options for those
patients whose tumors have become resistant to treatment,” said Marcia
Brose, M.D., Ph.D., Associate Professor of Otorhinolaryngology: Head and
Neck Surgery and Director of the Center for Rare Cancers at the Abramson
Cancer Center of the University of Pennsylvania, and principal
investigator of the trial. “These findings suggest that cabozantinib,
which showed encouraging efficacy and a manageable safety profile in
this phase 2 trial, may be a promising treatment option for this patient
population and warrants further evaluation.”
“We are dedicated to supporting investigator-sponsored trials focused on
evaluating cabozantinib in a range of tumor types to help inform our
ongoing development program whose main goal is to provide improved
treatment options to patients in need,” said Gisela Schwab, M.D.,
President, Product Development and Medical Affairs and Chief Medical
Officer, Exelixis. “Based on these promising results and data from other
studies of cabozantinib in previously treated DTC, Exelixis plans to
initiate a pivotal phase 3 study with cabozantinib in patients with
advanced DTC later this year.”
The most common treatment-related adverse events included hyperglycemia
(80 percent), diarrhea (77 percent), malaise/fatigue (74 percent), and
weight loss (71 percent). The majority of these adverse events were
grade 1 or 2. The most comment grade 3-5 adverse events occurring in
more than one patient included hypertension (14 percent), increased
lipase (9 percent), pulmonary embolism (6 percent), and hyponatremia (6
About the Trial
The IST is being conducted by the Center for Rare Cancers and
Personalized Therapy at the Abramson Cancer Center of the University of
Pennsylvania. Enrollment for the trial was completed in August 2017. Dr.
Marcia Brose, Associate Professor of Otorhinolaryngology: Head and Neck
Surgery, Perelman School of Medicine of the University of Pennsylvania
is the principal investigator. The median age of patients is 65 years
(range 45 to 84) and 17 patients (49 percent) are male. Of the patients
in the trial, 23 (66 percent) had papillary thyroid cancer, 3 (9
percent) had follicular (Hürthle cell) thyroid cancer and 9 (26 percent)
had poorly differentiated histology. Patients are administered oral
cabozantinib 60 mg once daily as long as they continue to derive
clinical benefit or until unacceptable drug-related toxicity. Sixteen
patients remain on the trial as of February 6, 2018.
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.4-6
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 and Switzerland for the
treatment of advanced RCC in adults who have received prior vascular
endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted
to European Medicines Agency (EMA) the regulatory dossier for
cabozantinib as a treatment for first-line advanced RCC in the European
Union on August 28, 2017; on September 8, 2017, Ipsen announced that the
EMA validated the application. 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 differentiated thyroid
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 lead
compounds, cabozantinib and cobimetinib, and advanced them into clinical
development before entering into partnerships with leading
biopharmaceutical companies in our efforts to bring these medicines 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.
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: Exelixis’ plans to initiate a
pivotal phase 3 trial with cabozantinib in patients with advanced DTC
later this year; the future presentation of data results from a phase 2
IST of cabozantinib for the first-line treatment of metastatic
radioiodine (RAI)-refractory DTC at the 2018 Multidisciplinary Head and
Neck Cancers Symposium; the clinical and therapeutic potential of
cabozantinib for patients with DTC; Exelixis’ continued support of ISTs
focused on evaluating cabozantinib in a range of tumor types; Exelixis’
goal to provide improved treatment options to patients in need; and
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. Words such as “plan,” “will,” “may,” “focused,”
“goal,” “potential,” “future,” “commitment,” “intend,” 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: the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; the availability of data at the
referenced times; Exelixis’ ability and the ability of its collaborators
to conduct clinical trials of cabozantinib sufficient to achieve a
positive completion; the complexities and challenges associated with
regulatory review and approval processes; 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’
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.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
American Cancer Society. Key Statistics for Thyroid Cancer. https://www.cancer.org/cancer/thyroid-cancer/about/key-statistics.html.
Accessed January 2018.
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.
Worden F. 2014. Treatment strategies for radioactive iodine-refractory
differentiated thyroid cancer. Ther Adv Med Oncol 6:267–279.
Xing M, Haugen BR, Schlumberger M. 2013. Progress in molecular-based
management of differentiated thyroid cancer. Lancet
Pacini F, et al. 2012. Radioactive iodine-refractory differentiated
thyroid cancer: unmet needs and future directions. Expert Rev
Endocrinol Metab 7:541–554.
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
EVP, Public Affairs and Investor Relations
Director, Public Affairs and Advocacy