– After more than five years of follow-up,
CABOMETYX in combination with Opdivo continued to show survival
benefit compared with sunitinib –
– Long-term efficacy seen across subgroups,
including site of metastases –
Exelixis, Inc. (Nasdaq: EXEL) today announced final results from
the phase 3 CheckMate -9ER pivotal trial evaluating CABOMETYX®
(cabozantinib) in combination with Opdivo® (nivolumab) versus
sunitinib for patients with previously untreated advanced renal
cell carcinoma (RCC). After more than five years of follow-up, the
findings demonstrated that efficacy benefits with CABOMETYX in
combination with Opdivo were sustained long term. These results,
including subgroup analyses, will be presented at 8:10 a.m. PT on
February 15 during Oral Abstract Session C: Renal Cell Cancer and
Testicular Cancer at the American Society of Clinical Oncology 2025
Genitourinary Cancers Symposium (ASCO GU).
“In this evolving treatment landscape for renal cell carcinoma,
patients are looking for options that have shown improved survival
time in the long-term,” said Robert J. Motzer, M.D., Kidney Cancer
Section Head, Genitourinary Oncology Service, Memorial Sloan
Kettering Cancer Center. “These final five-year results from
CheckMate -9ER demonstrated the durable clinical benefits of
cabozantinib in combination with nivolumab—including for those with
organ metastases or intermediate- or poor-risk disease
classifications—and continue to support this combination regimen as
a valuable first-line option for this patient population.”
At a median follow-up of 67.6 months, CABOMETYX in combination
with Opdivo improved progression-free survival (PFS; hazard ratio
[HR]: 0.58; 95% confidence interval [CI]: 0.49-0.70) and overall
survival (OS; HR: 0.79; 95% CI: 0.65-0.96) compared with sunitinib
in the intent-to-treat population. A subgroup analysis by
International Metastatic RCC Database Consortium (IMDC) risk showed
PFS and objective response rates (ORR) favored CABOMETYX in
combination with Opdivo versus sunitinib regardless of IMDC risk
group. Detailed results are shown in Table 1.
Table 1
CABOMETYX + Opdivo
Sunitinib
ITT population (n=651)
Median PFS, mo
16.4
8.3
PFS HR (95% CI)
0.58 (0.49-0.70)
Median OS, mo
46.5
35.5
OS HR (95% CI)
0.79 (0.65-0.96)
ORR, %
55.7
27.4
DOR, mo
22.0
15.2
Favorable IMDC risk
(n=146)
Median PFS, mo
21.4
12.8
PFS HR (95% CI)
0.67 (0.46-0.97)
Median OS, mo
53.7
58.9
OS HR (95% CI)
1.08 (0.70-1.66)
ORR, %
66.2
43.1
Intermediate/poor IMDC risk
(n=505)
Median PFS, mo
15.4
7.1
PFS HR (95% CI)
0.56 (0.46-0.69)
Median OS, mo
43.9
29.2
OS HR (95% CI)
0.74 (0.60-0.92)
ORR, %
52.6
23.0
CI: confidence interval; DOR: duration of
response; HR: hazard ratio; IMDC: International Metastatic RCC
Database Consortium; ITT: intent-to-treat; ORR: objective response
rate; OS: overall survival; PFS: progression-free survival
In an analysis by baseline metastases sites, PFS, OS and ORR
favored the combination regimen versus sunitinib in all three
subgroups (liver, bone and lung). Detailed results are shown in
Table 2.
Table 2
Liver
Bone
Lung
CABOMETYX + Opdivo
(n=73)
Sunitinib (n=56)
CABOMETYX + Opdivo
(n=79)
Sunitinib (n=75)
CABOMETYX + Opdivo
(n=241)
Sunitinib (n=251)
Median PFS, mo
10.9
6.2
13.8
5.3
16.4
8.3
PFS HR (95% CI)
0.55 (0.37-0.82)
0.43 (0.30-0.64)
0.56 (0.46-0.69)
Median OS, mo
37.6
22.1
34.8
20.7
47.5
32.4
OS HR (95% CI)
0.65 (0.43-0.97)
0.66 (0.45-0.95)
0.75 (0.60-0.94)
ORR, %
52.1
21.4
49.4
9.3
57.3
27.9
CI: confidence interval; HR: hazard ratio;
IMDC: ORR: objective response rate; OS: overall survival; PFS:
progression-free survival
“With now more than five years of follow-up, these results
continue to support CABOMETYX in combination with Opdivo as a
treatment regimen that can have enduring survival benefits for
patients with previously untreated advanced kidney cancer,” said
Amy Peterson, M.D., Executive Vice President, Product Development
& Medical Affairs, and Chief Medical Officer, Exelixis. “The
efficacy was sustained across multiple subgroups, further
underscoring the potential of this regimen to benefit a broad
population with variable disease burden. We are proud to have
established such a compelling standard of care for this community
and remain committed to developing much-needed treatment options
for all patients living with advanced cancers.”
Safety and tolerability with long-term follow-up were manageable
and consistent with previous analyses. No new safety signals were
reported. Grade 3/4 adverse events (AEs) occurred in 68% of
patients treated with CABOMETYX in combination with Opdivo versus
55% of patients treated with sunitinib, with the most frequent
being diarrhea (7% versus 5%, respectively), palmar-plantar
erythrodysesthesia (8% versus 8%), hypertension (13% versus 13%),
fatigue (3% versus 5%), thrombocytopenia (<1% versus 5%) and
alanine aminotransferase increased (6% versus 1%). One
treatment-related death per investigator occurred with CABOMETYX in
combination with Opdivo versus three with sunitinib.
Treatment-related AEs leading to discontinuation occurred in 28% of
patients treated with CABOMETYX in combination with Opdivo versus
11% of patients treated with sunitinib.
About CheckMate -9ER CheckMate -9ER is an open-label,
randomized, multi-national phase 3 trial evaluating patients with
previously untreated advanced or metastatic RCC. A total of 651
patients (23% favorable risk, 58% intermediate risk, 20% poor risk;
25% tumor PD-L1≥1%) were randomized to receive CABOMETYX in
combination with Opdivo (n=323) versus sunitinib (n=328). The
primary endpoint is PFS. Secondary endpoints include OS and ORR.
The primary efficacy analysis is comparing the doublet combination
versus sunitinib in all randomized patients. The trial is sponsored
by Bristol Myers Squibb and Ono Pharmaceutical Co. and co-funded by
Exelixis, Inc., Ipsen Pharma SAS and Takeda Pharmaceutical Company
Limited.
About RCC Kidney cancer is among the top ten most
commonly diagnosed forms of cancer among both men and women in the
U.S.1 An estimated 80,980 Americans will be diagnosed with kidney
cancer in 2025.1 If detected in its early stages, the five-year
survival rate for RCC is high; for patients with advanced or
late-stage metastatic RCC, however, the five-year survival rate is
only 18%.2 In 2024, approximately 33,200 patients with advanced
kidney cancer required systemic therapy in the U.S., with over
21,000 patients receiving first-line treatment.3
About CABOMETYX® (cabozantinib) In the U.S.,
CABOMETYX tablets are approved as monotherapy for the treatment of
patients with advanced RCC and in combination with nivolumab 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.
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
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 final results from the
CheckMate -9ER trial at ASCO GU 2025; the therapeutic potential of
cabozantinib in combination with nivolumab and Exelixis’ belief
that the regimen may provide enduring survival benefits for
patients with previously untreated advanced kidney cancer;
Exelixis’ belief in the ability of the regimen to benefit a broad
population with variable disease burden; Exelixis’ commitment to
developing much-needed treatment options for all patients living
with advanced cancers; 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’
and Bristol Myers Squibb’s continuing compliance with applicable
legal and regulatory requirements; the potential failure of
cabozantinib in combination with nivolumab 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’ and Bristol Myers Squibb’s
ability to protect their respective 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 Cancer Facts
& Figures 2025. ACS. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2025/2025-cancer-facts-and-figures-acs.pdf.
Accessed February 2025. 2 Survival Rates for Kidney Cancer. ACS.
Available at:
https://www.cancer.org/cancer/types/kidney-cancer/detection-diagnosis-staging/survival-rates.html.
Accessed February 2025. 3 Citeline’s Datamonitor Healthcare: Renal
Cell Carcinoma. March 2023 (internal data on file).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250214191927/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
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