– CABINET trial will be unblinded and stopped
early due to a dramatic improvement in efficacy per a unanimous
recommendation by The Alliance for Clinical Trials in Oncology
independent Data and Safety Monitoring Board –
– Based on positive results, findings will be
discussed with the U.S. Food and Drug Administration –
Exelixis, Inc. (Nasdaq: EXEL) today announced that the Alliance
for Clinical Trials in Oncology independent Data and Safety
Monitoring Board (DSMB) unanimously recommended to unblind and stop
the phase 3 CABINET pivotal trial early due to a dramatic
improvement in efficacy that was observed at an interim analysis.
CABINET is evaluating cabozantinib (CABOMETYX®) compared with
placebo in patients with either advanced pancreatic neuroendocrine
tumors (pNET) or advanced extra-pancreatic neuroendocrine tumors
(also referred to as carcinoid tumors) who experienced progression
after prior systemic therapy. Cabozantinib substantially prolonged
the time without disease progression or death in both of the
trial’s cohorts. CABINET is sponsored by the National Cancer
Institute (NCI) and is led by The Alliance for Clinical Trials in
Oncology. Detailed findings will be presented at an upcoming
medical meeting and discussed with the U.S. Food and Drug
Administration (FDA).
“As there is no standard of care for patients with advanced
pancreatic or extra-pancreatic neuroendocrine tumors whose disease
has progressed after prior therapy, we are pleased to see that
cabozantinib improved outcomes for two additional patient
populations living with advanced, difficult-to-treat cancers,” said
Will Berg, M.D., Senior Vice President, Medical Affairs, Exelixis.
“We are grateful for the recommendation of the Data and Safety
Monitoring Board to unblind the CABINET study early due to a
dramatic improvement in efficacy and look forward to discussing
these findings with the U.S. Food and Drug Administration.”
The safety profile of cabozantinib observed in the trial was
consistent with its known safety profile, and no new safety signals
were identified.
“Patients with progressive neuroendocrine tumors have limited
treatment options. At present, after progression on previous
therapies, the treatment path is unclear, underscoring the need for
additional options for this disease that is rising in incidence,”
said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial
and Clinical Director of the Gastrointestinal Cancer Center and
Director of the Program in Carcinoid and Neuroendocrine Tumors at
Dana-Farber Cancer Institute. “These promising findings from the
CABINET trial, in which cabozantinib showed an efficacy benefit for
patients with pancreatic and extra-pancreatic neuroendocrine
tumors, are welcome news and show the potential for cabozantinib to
address important unmet needs for this community.”
About CABINET (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 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 with the NCI’s Cancer Therapy Evaluation
Program. CABINET is a multicenter, randomized, double-blinded,
placebo-controlled phase 3 pivotal trial that enrolled a total of
290 patients in two separate cohorts (pNET, n=93; extra-pancreatic
NET, n=197) in the U.S. Patients were randomized 2:1 into the
cabozantinib or placebo arms of the study in each of the two
cohorts. Patients must have had measurable disease per RECIST 1.1
criteria and must have experienced disease progression after at
least one FDA-approved line of prior therapy other than
somatostatin analogs. The primary endpoint was progression-free
survival in each cohort. Upon confirmation of disease progression,
patients were unblinded, and those receiving placebo were permitted
to cross over to open-label therapy with cabozantinib. Secondary
endpoints included overall survival, radiographic response rate and
safety. More information about this trial is available at
ClinicalTrials.gov.
About NET
NET refer to 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 the U.S.,
more than 12,000 people are diagnosed with NET each year and
approximately 171,000 people are living with the disease.2 The
number of people diagnosed with NET each year has been increasing.2
NET are classified as functional or non-functional.1 Functional NET
release peptide hormones that can cause debilitating symptoms and
necessitate treatment, while symptoms of non-functional NET are
related primarily to tumor growth.1,3,4 Most NET take years to
develop and grow slowly, but some grow quickly.5 NET can develop in
any part of the body, but most commonly start in the
gastrointestinal (GI) tract or in the lungs – these historically
have been referred to as carcinoid tumors.5 The five-year survival
rates for advanced GI-NET and lung carcinoid tumors are 68% and
55%, respectively.6,7 NET can also start in the pancreas.8 While
less common, these NET can be more aggressive and the five-year
survival rate for advanced pNET is only 23%.8,9 Surgery to remove
the tumor and prevent it from spreading is the typical first
approach to treatment for both carcinoid tumors and pNET.10 For
more advanced disease, options include somatostatin analogs,
targeted therapy, peptide-receptor radionuclide therapy and
chemotherapy.10
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of
patients with advanced renal cell carcinoma (RCC); for the
treatment of patients with hepatocellular carcinoma (HCC) who have
been previously treated with sorafenib; for patients with advanced
RCC as a first-line treatment in combination with nivolumab; 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 the European Union and
additional countries and regions worldwide. 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 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,
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 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 bi-coastal centers of 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 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
therapeutic potential of cabozantinib to reduce the risk of disease
progression or death for patients with advanced pancreatic
neuroendocrine tumors or advanced extra-pancreatic neuroendocrine
tumors who experienced progression after prior systemic therapy;
Exelixis’ plans to discuss the trial data from CABINET with the
U.S. Food and Drug Administration; 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: 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; Exelixis’ dependence on its
relationships with its cabozantinib commercial collaboration
partners; 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 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, 2023 and Annual Report
on Form 10-K filed with the SEC on February 7, 2023, 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, except as required by law.
Exelixis, the Exelixis logo and CABOMETYX are
registered U.S. trademarks of Exelixis.
1 Neuroendocrine Tumors: Introduction. Cancer.Net website.
Available at:
https://www.cancer.net/cancer-types/neuroendocrine-tumors/introduction.
Accessed August 2023. 2 Neuroendocrine Tumors: Statistics.
Cancer.Net website. Available at:
https://www.cancer.net/cancer-types/neuroendocrine-tumors/statistics.
Accessed August 2023. 3 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 August 2023. 4 Neuroendocrine Tumors: Types of Treatment.
Cancer.Net website. Available at:
https://www.cancer.net/cancer-types/neuroendocrine-tumors/types-treatment.
Accessed August 2023. 5 Neuroendocrine Tumor of the
Gastrointestinal Tract: Introduction. Cancer.Net website. Available
at:
https://www.cancer.net/cancer-types/neuroendocrine-tumor-gastrointestinal-tract/introduction.
Accessed August 2023. 6 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 August 2023. 7 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 August 2023. 8 Neuroendocrine Tumor of the Pancreas:
Statistics. Cancer.Net website. Available at:
https://www.cancer.net/cancer-types/neuroendocrine-tumor-pancreas/statistics.
Accessed August 2023. 9 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 August 2023. 10 Neuroendocrine Tumor (NET). NCI website.
Availably at:
https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor.
Accessed August 2023.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230823099737/en/
Investors Contact: Susan Hubbard EVP, Public Affairs and
Investor Relations Exelixis, Inc. (650) 837-8194
shubbard@exelixis.com
Media Contact: Claire McConnaughey Senior Director,
Public Affairs Exelixis, Inc. (650) 837-7052
cmcconn@exelixis.com
Exelixis (NASDAQ:EXEL)
Gráfico Histórico do Ativo
De Mai 2024 até Jun 2024
Exelixis (NASDAQ:EXEL)
Gráfico Histórico do Ativo
De Jun 2023 até Jun 2024