– Cabozantinib reduced the risk of disease
progression or death by 50 percent compared with placebo in
patients with advanced gastrointestinal neuroendocrine tumors
–
– Supplemental New Drug Application under
review with the U.S. FDA for cabozantinib for the treatment of
patients with advanced neuroendocrine tumors based on findings from
CABINET –
Exelixis, Inc. (Nasdaq: EXEL) today announced results from a
subgroup analysis of the phase 3 CABINET pivotal study of patients
with extra-pancreatic neuroendocrine tumors (epNET) arising in the
gastrointestinal (GI) tract. The analysis showed cabozantinib was
associated with an improvement in progression-free survival (PFS)
compared with placebo in patients with advanced GI neuroendocrine
tumors (NET), which was a subgroup of the epNET cohort. These
results are being presented today during Poster Session B: Cancers
of the Pancreas, Small Bowel, and Hepatobiliary Tract, at 11:30
a.m. PT on January 24 at the American Society of Clinical Oncology
2025 Gastrointestinal Cancers Symposium (ASCO GI 2025).
“Treating neuroendocrine tumors after disease progression can be
challenging, including for those with tumors in the
gastrointestinal tract, as treatment options are limited,” said
Jonathan Strosberg, M.D., President Emeritus, North American
Neuroendocrine Tumor Society and Chair, GI Research Program,
Moffitt Cancer Center and Research Institute. “This subgroup
analysis from the CABINET study showed that cabozantinib improved
progression-free survival for patients with tumors arising in the
GI tract and provides a more detailed picture of how patients with
the most common form of this cancer may benefit from this
treatment. As a physician, I’m encouraged by these findings, as
they suggest cabozantinib has potential to become a standard of
care for patients greatly in need of new options.”
This subgroup analysis included 116 of the 203 patients in the
epNET cohort. The most common primary tumor locations were
ileum/cecum (54%), small intestine with location not specified
(20%), non-cecum colon or rectum (11%), stomach (4%), duodenum
(3%), jejunum (3%) and non-specified midgut site (3%).
Cabozantinib was associated with improved PFS by blinded
independent central review compared with placebo for patients with
GI NET (hazard ratio: 0.50; 95% confidence interval: 0.28-0.88;
one-sided stratified log-rank P=0.007). Median PFS was 8.5 months
with cabozantinib compared with 5.6 months with placebo.
Cabozantinib demonstrated potential benefit across clinical
factors, including grade, functional status, concurrent
somatostatin agent use, and prior therapy with Lu-177 dotatate or
everolimus. One patient achieved a partial response with
cabozantinib versus none with placebo, and 48 versus 30 patients,
respectively, achieved stable disease.
“These new data add to the robust results from the CABINET trial
that demonstrate the benefits of cabozantinib across a wide range
of patients with neuroendocrine tumors and further underscore the
potential of cabozantinib to become a much-needed new option for
those with GI NET, which accounts for the majority of real-world
patients with this tumor type,” said Amy Peterson, M.D., Executive
Vice President, Product Development & Medical Affairs, and
Chief Medical Officer, Exelixis. “We look forward to continuing to
work with the U.S. FDA as they review our regulatory application
for cabozantinib for the treatment of patients with previously
treated advanced neuroendocrine tumors.”
The safety profile of cabozantinib observed in patients with GI
NET was consistent with its known safety profile; no new safety
signals were identified. The most frequent grade 3/4 adverse events
included hypertension (19% of patients receiving cabozantinib and
4% receiving placebo), diarrhea (13% and 4%, respectively) and
fatigue (10% and 4%). Three grade 5 events occurred in the
cabozantinib arm possibly related to cabozantinib: one due to
cardiac arrest and two not specified.
As announced in August 2023, the Alliance for Clinical Trials in
Oncology independent Data and Safety Monitoring Board unanimously
recommended that the CABINET trial be stopped early and unblinded
due to the substantial improvement in PFS observed at an interim
analysis. Final PFS results were presented at the 2024 European
Society of Medical Oncology Congress and published concurrently in
the New England Journal of Medicine. In August 2024, Exelixis
announced that the U.S. Food and Drug Administration (FDA) had
accepted the supplemental New Drug Application (sNDA) for
cabozantinib for the treatment of previously treated, advanced NET
and assigned a Prescription Drug User Fee Act target action date of
April 3, 2025.
About CABINET (Alliance A021602)
CABINET (Randomized, Double-Blinded Phase III Study of
CABozantinib versus Placebo In Patients with Advanced
NEuroendocrine Tumors After Progression on Prior
Therapy) is sponsored by the National Cancer Institute (NCI), part
of the National Institutes of Health, and is being led and
conducted by the NCI-funded Alliance for Clinical Trials in
Oncology with participation from the NCI-funded National Clinical
Trials Network as part of Exelixis’ collaboration through a
Cooperative Research and Development Agreement with the NCI’s
Cancer Therapy Evaluation Program.
CABINET is a multicenter, randomized, double-blinded,
placebo-controlled phase 3 pivotal trial that had enrolled a total
of 298 patients in the U.S at the time of the final analysis.
Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in
two separately powered cohorts (pancreatic NET, n=95; epNET,
n=203). The epNET cohort included patients with the following
primary tumor sites: GI tract, lung, unknown primary sites, and
other organs. Each cohort was randomized separately and had its own
statistical analysis plan. Patients must have had measurable
disease per RECIST 1.1 criteria and must have experienced disease
progression or intolerance after at least one U.S. FDA-approved
line of prior systemic therapy other than somatostatin analogs. The
primary endpoint in each cohort was PFS per RECIST 1.1 by blinded
independent central review. Secondary endpoints included overall
survival, objective response rate and safety. More information
about this trial is available at ClinicalTrials.gov.
About NET
NET are cancers that begin in the specialized cells of the
body’s neuroendocrine system.1 These cells have traits of both
hormone-producing endocrine cells and nerve cells.1 In 2024, the
estimated prevalence of NET in the U.S. was more than 380,000
people.2 It is estimated that 161,000 to 192,000 people are living
with unresectable, locally advanced or metastatic NET.2 The number
of people diagnosed with NET has been increasing in recent
decades.3 Functional NET release peptide hormones that can cause
debilitating symptoms, like diarrhea, hypertension and flushing,
which may require focused treatment, while symptoms of
non-functional NET are related primarily to tumor growth.4,5 Most
NET take years to develop and grow slowly, but eventually all
patients with advanced or metastatic NET will develop refractory
and progressing disease.6,7
NET can develop in any part of the body, but most commonly start
in the GI tract or in the lungs, where they have historically been
referred to as carcinoid tumors and are more recently called
epNET.1 The five-year survival rates for advanced GI and lung NET
tumors are 68% and 55%, respectively.8,9 NET can also start in the
pancreas, where they tend to be more aggressive, with a five-year
survival rate of only 23% for advanced disease.1,10 For advanced
NET patients, treatment options include somatostatin analogs,
chemotherapy, molecular targeted therapy and peptide-receptor
radionuclide therapy.11
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved as monotherapy for
the treatment of patients with advanced renal cell carcinoma (RCC)
and in combination with nivolumab for patients as a first-line
treatment for patients with advanced RCC; for the treatment of
patients with hepatocellular carcinoma (HCC) who have been
previously treated with sorafenib, and; for adult and pediatric
patients 12 years of age and older with locally advanced or
metastatic differentiated thyroid cancer (DTC) that has progressed
following prior VEGFR-targeted therapy and who are radioactive
iodine-refractory or ineligible. CABOMETYX tablets have also
received regulatory approvals in over 65 countries outside the U.S.
and Japan, including the European Union. In 2016, Exelixis granted
Ipsen Pharma SAS exclusive rights for the commercialization and
further clinical development of cabozantinib outside of the U.S.
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. Exelixis holds the exclusive rights to
develop and commercialize cabozantinib in the U.S.
CABOMETYX is not indicated as a treatment for NET.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Severe and fatal hemorrhages occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue
CABOMETYX for Grade 3 or 4 hemorrhage and prior to surgery as
recommended. Do not administer CABOMETYX to patients who have a
recent history of hemorrhage, including hemoptysis, hematemesis, or
melena.
Perforations and Fistulas: Fistulas, including fatal
cases, occurred in 1% of CABOMETYX patients. Gastrointestinal (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Monitor patients for signs and symptoms of fistulas and
perforations, including abscess and sepsis. Discontinue CABOMETYX
in patients who experience a Grade 4 fistula or a GI
perforation.
Thrombotic Events: CABOMETYX increased the risk of
thrombotic events. Venous thromboembolism occurred in 7% (including
4% pulmonary embolism) and arterial thromboembolism in 2% of
CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX
patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic
events that require medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause
hypertension, including hypertensive crisis. Hypertension was
reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX
patients. Do not initiate CABOMETYX in patients with uncontrolled
hypertension. Monitor blood pressure regularly during CABOMETYX
treatment. Withhold CABOMETYX for hypertension that is not
adequately controlled with medical management; when controlled,
resume at a reduced dose. Permanently discontinue CABOMETYX for
severe hypertension that cannot be controlled with
anti-hypertensive therapy or for hypertensive crisis.
Diarrhea: Diarrhea occurred in 62% of CABOMETYX patients.
Grade 3 diarrhea occurred in 10% of CABOMETYX patients. Monitor and
manage patients using antidiarrheals as indicated. Withhold
CABOMETYX until improvement to ≤ Grade 1, resume at a reduced
dose.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
45% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX
patients. Withhold CABOMETYX until improvement to Grade 1 and
resume at a reduced dose for intolerable Grade 2 PPE or Grade 3
PPE.
Hepatotoxicity: CABOMETYX in combination with nivolumab
can cause hepatic toxicity with higher frequencies of Grades 3 and
4 ALT and AST elevations compared to CABOMETYX alone.
Monitor liver enzymes before initiation of and periodically
throughout treatment. Consider more frequent monitoring of liver
enzymes than when the drugs are administered as single agents. For
elevated liver enzymes, interrupt CABOMETYX and nivolumab and
consider administering corticosteroids.
With the combination of CABOMETYX and nivolumab, Grades 3 and 4
increased ALT or AST were seen in 11% of patients. ALT or AST >3
times ULN (Grade ≥2) was reported in 83 patients, of whom 23 (28%)
received systemic corticosteroids; ALT or AST resolved to Grades
0-1 in 74 (89%). Among the 44 patients with Grade ≥2 increased ALT
or AST who were rechallenged with either CABOMETYX (n=9) or
nivolumab (n=11) as a single agent or with both (n=24), recurrence
of Grade ≥2 increased ALT or AST was observed in 2 patients
receiving CABOMETYX, 2 patients receiving nivolumab, and 7 patients
receiving both CABOMETYX and nivolumab. Withhold and resume at a
reduced dose based on severity.
Adrenal Insufficiency: CABOMETYX in combination with
nivolumab can cause primary or secondary adrenal insufficiency. For
Grade 2 or higher adrenal insufficiency, initiate symptomatic
treatment, including hormone replacement as clinically indicated.
Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a
reduced dose depending on severity.
Adrenal insufficiency occurred in 4.7% (15/320) of patients with
RCC who received CABOMETYX with nivolumab, including Grade 3
(2.2%), and Grade 2 (1.9%) adverse reactions. Adrenal insufficiency
led to permanent discontinuation of CABOMETYX and nivolumab in 0.9%
and withholding of CABOMETYX and nivolumab in 2.8% of patients with
RCC.
Approximately 80% (12/15) of patients with adrenal insufficiency
received hormone replacement therapy, including systemic
corticosteroids. Adrenal insufficiency resolved in 27% (n=4) of the
15 patients. Of the 9 patients in whom CABOMETYX with nivolumab was
withheld for adrenal insufficiency, 6 reinstated treatment after
symptom improvement; of these, all (n=6) received hormone
replacement therapy and 2 had recurrence of adrenal
insufficiency.
Proteinuria: Proteinuria was observed in 8% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until
improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced
dose. Discontinue CABOMETYX in patients who develop nephrotic
syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of
CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration or erosion, persistent jaw pain, or slow
healing of the mouth or jaw after dental surgery. Perform an oral
examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices.
Withhold CABOMETYX for at least 3 weeks prior to scheduled dental
surgery or invasive dental procedures, if possible. Withhold
CABOMETYX for development of ONJ until complete resolution, resume
at a reduced dose.
Impaired Wound Healing: Wound complications occurred with
CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to
elective surgery. Do not administer CABOMETYX for at least 2 weeks
after major surgery and until adequate wound healing. The safety of
resumption of CABOMETYX after resolution of wound healing
complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
RPLS, a syndrome of subcortical vasogenic edema diagnosed by
characteristic findings on MRI, can occur with CABOMETYX. Evaluate
for RPLS in patients presenting with seizures, headache, visual
disturbances, confusion, or altered mental function. Discontinue
CABOMETYX in patients who develop RPLS.
Thyroid Dysfunction: Thyroid dysfunction, primarily
hypothyroidism, has been observed with CABOMETYX. Based on the
safety population, thyroid dysfunction occurred in 19% of patients
treated with CABOMETYX, including Grade 3 in 0.4% of patients.
Patients should be assessed for signs of thyroid dysfunction
prior to the initiation of CABOMETYX and monitored for signs and
symptoms of thyroid dysfunction during CABOMETYX treatment. Thyroid
function testing and management of dysfunction should be performed
as clinically indicated.
Hypocalcemia: CABOMETYX can cause hypocalcemia. Based on
the safety population, hypocalcemia occurred in 13% of patients
treated with CABOMETYX, including Grade 3 in 2% and Grade 4 in 1%
of patients. Laboratory abnormality data were not collected in
CABOSUN.
In COSMIC-311, hypocalcemia occurred in 36% of patients treated
with CABOMETYX, including Grade 3 in 6% and Grade 4 in 3% of
patients.
Monitor blood calcium levels and replace calcium as necessary
during treatment. Withhold and resume at reduced dose upon recovery
or permanently discontinue CABOMETYX depending on severity.
Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Verify the pregnancy status of females
of reproductive potential prior to initiating CABOMETYX and advise
them to use effective contraception during treatment and for 4
months after the last dose.
ADVERSE REACTIONS
The most common (≥20%) adverse reactions are:
CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased
appetite, hypertension, nausea, vomiting, weight decreased, and
constipation.
CABOMETYX in combination with nivolumab: diarrhea, fatigue,
hepatotoxicity, PPE, stomatitis, rash, hypertension,
hypothyroidism, musculoskeletal pain, decreased appetite, nausea,
dysgeusia, abdominal pain, cough, and upper respiratory tract
infection.
DRUG INTERACTIONS
Strong CYP3A4 Inhibitors: If coadministration with strong
CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong
CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St. John’s wort.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during
CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic
impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in
patients with severe hepatic impairment.
Please see accompanying full Prescribing Information
https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit
http://www.fda.gov/medwatch or call
1-800-FDA-1088.
About Exelixis
Exelixis is a globally ambitious oncology company innovating
next-generation medicines and regimens at the forefront of cancer
care. Powered by drug discovery and development excellence, we are
rapidly evolving our product portfolio to target an expanding range
of tumor types and indications with our clinically differentiated
pipeline of small molecules, antibody-drug conjugates and other
biotherapeutics. This comprehensive approach harnesses decades of
robust investment in our science and partnerships to advance our
investigational programs and extend the impact of our flagship
commercial product, CABOMETYX® (cabozantinib). Exelixis is driven
by a bold scientific pursuit to create transformational treatments
that give more patients hope for the future. For information about
the company and its mission to help cancer patients recover
stronger and live longer, visit www.exelixis.com, follow
@ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and
follow Exelixis on LinkedIn.
Forward-Looking Statements
This press release contains forward-looking statements,
including, without limitation, statements related to: the
presentation of detailed results from the CABINET trial at ASCO GI
2025; the therapeutic potential of cabozantinib as a treatment
across a wide range of patients with neuroendocrine tumors and the
potential of cabozantinib to become a much-needed new option for
those with GI NET; the regulatory review process with respect to
Exelixis’ sNDA for cabozantinib in previously treated advanced NET,
including the Prescription Drug User Fee Act target action date
assigned by the FDA; and Exelixis’ scientific pursuit to create
transformational treatments that give more patients hope for the
future. 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: the availability of data at the referenced
times; complexities and the unpredictability of the regulatory
review and approval processes in the U.S. and elsewhere; Exelixis’
continuing compliance with applicable legal and regulatory
requirements; the potential failure of cabozantinib to demonstrate
safety and/or efficacy in future clinical testing; unexpected
concerns that may arise as a result of the occurrence of adverse
safety events or additional data analyses of clinical trials
evaluating cabozantinib; the costs of conducting clinical trials;
Exelixis’ dependence on third-party vendors for the development,
manufacture and supply of cabozantinib; Exelixis’ ability to
protect its intellectual property rights; market competition,
including the potential for competitors to obtain approval for
generic versions of CABOMETYX; changes in economic and business
conditions; and other factors affecting Exelixis and its
development programs detailed from time to time under the caption
“Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K
and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’
future filings with the Securities and Exchange Commission. 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, except as required
by law.
Exelixis, the Exelixis logo and CABOMETYX are
registered U.S. trademarks of Exelixis.
# # #
_______________________________
1 Neuroendocrine Tumors. Cleveland Clinic
website. Available at:
https://my.clevelandclinic.org/health/diseases/22006-neuroendocrine-tumors-net.
Accessed January 2025.
2 Population Estimate: Unresectable,
Locally Advanced or Metastatic Extra-Pancreatic NET. June 2024
(internal data on file).
3 Pathak, S., Starr, J.S., Halfdanarson
T., et al. Understanding the increasing incidence of neuroendocrine
tumors. Expert Rev Endocrinol Metab. September
2023;18(5):377-385.
4 Pancreatic Neuroendocrine Tumors (Islet
Cell Tumors) Treatment (PDQ®)–Patient Version. NCI website.
Available at:
https://www.cancer.gov/types/pancreatic/patient/pnet-treatment-pdq.
Accessed January 2025.
5 What Is a Pancreatic Neuroendocrine
Tumor? ACS website. Available at:
https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/about/what-is-pnet.html.
Accessed January 2025.
6 McClellan, K., Chen. E.Y, Kardosh A., et
al. Therapy Resistant Gastroenteropancreatic Neuroendocrine Tumors.
Cancers. 2022, 14(19), 4769.
7 What is a Gastrointestinal Carcinoid
Tumor? ACS website. Available at:
https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/about/what-is-gastrointestinal-carcinoid.html.
Accessed January 2025.
8 Survival Rates for Gastrointestinal
Carcinoid Tumors. ACS website. Available at:
https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html.
Accessed January 2025.
9 Survival Rates for Lung Carcinoid
Tumors. ACS website. Available at:
https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html.
Accessed January 2025.
10 Survival Rates for Pancreatic
Neuroendocrine Tumor. ACS website. Available at:
https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html.
Accessed January 2025.
11 Neuroendocrine Tumor (NET). NCI
website. Available at:
https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor.
Accessed January 2025.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250123418184/en/
Investors: Susan Hubbard EVP, Public Affairs and Investor
Relations Exelixis, Inc. (650) 837-8194 shubbard@exelixis.com
Media: Claire McConnaughey Senior Director, Public
Affairs Exelixis, Inc. (650) 837-7052 cmcconn@exelixis.com
Exelixis (NASDAQ:EXEL)
과거 데이터 주식 차트
부터 1월(1) 2025 으로 2월(2) 2025
Exelixis (NASDAQ:EXEL)
과거 데이터 주식 차트
부터 2월(2) 2024 으로 2월(2) 2025
