– Data from the CheckMate 040 trial
presented at the 2020 American Society of Clinical Oncology’s
Gastrointestinal Cancers Symposium –
Exelixis, Inc. (NASDAQ: EXEL) today announced phase 1/2 clinical
trial results from the combination of cabozantinib (CABOMETYX®) and
nivolumab (Opdivo®) with or without ipilimumab (Yervoy®) in
advanced hepatocellular carcinoma (HCC). Data from the cabozantinib
combination cohort of the CheckMate 040 trial will be presented on
Friday, January 24 during Rapid Abstract Session B from 7:00 – 7:45
a.m. PT at the 2020 American Society of Clinical Oncology’s
Gastrointestinal Cancers Symposium (ASCO GI), which is being held
in San Francisco, California, January 23-25, 2020. The data will
also be included in Poster Session B from 12:00 – 1:30 p.m. PT and
4:30 – 5:30 p.m. PT on January 24.
CheckMate 040 is a phase 1/2 study that includes an exploratory
cohort of patients with advanced HCC who were either treatment
naïve (41%) or who were intolerant to or had progressed on prior
sorafenib therapy (59%). For the 36 patients treated with the
combination of cabozantinib and nivolumab (17 treatment naïve [47%]
and 19 with prior sorafenib therapy [53%]), the
investigator-assessed objective response rate (ORR) was 19%, and
disease control rate (DCR) was 75%. Median progression-free
survival (PFS) was 5.4 months, and median overall survival was 21.5
months. For the 35 patients treated with the combination of
cabozantinib, nivolumab and ipilimumab (12 treatment naïve [34%]
and 23 with prior sorafenib therapy [66%]), the
investigator-assessed ORR was 29%, and DCR was 83%. Median PFS was
6.8 months, and median overall survival had not yet been
reached.
“We are pleased to report clinically meaningful responses from
CheckMate 040 cohort 6 in advanced liver cancer patients treated
with these cabozantinib combinations,” said Thomas Yau, M.D.,
Clinical Associate Professor, Department of Medicine, The
University of Hong Kong, and a lead investigator of the trial.
“Patients with advanced liver cancer need new and effective
treatment options. Based on the cohort six findings, cabozantinib
in combination with immunotherapy offers a potentially powerful and
attractive new treatment approach that warrants further study in
advanced liver cancer populations.”
No new safety signals were identified in this combination
cohort. Treatment-related grade 3 or 4 adverse events were observed
in 47% of the cabozantinib and nivolumab group; events occurring in
more than 5% of patients were hypertension (11%), diarrhea (11%),
aspartate aminotransferase (AST) increase (8%) and lipase increase
(6%). Treatment-related grade 3 or 4 adverse events were observed
in 71% of the cabozantinib, nivolumab and ipilimumab group; events
occurring in more than 5% of patients were AST increase (23%),
lipase increase (17%), ALT increase (17%), hypertension (17%) and
palmar-plantar erythrodysaesthesia (9%). Discontinuation rates due
to treatment-related adverse events were 11% for the cabozantinib
and nivolumab group and 20% for the cabozantinib, nivolumab and
ipilimumab group.
“As we just marked one year since CABOMETYX was approved for the
treatment of patients with advanced hepatocellular cancer who have
previously received sorafenib, it’s exciting to be sharing new data
featuring cabozantinib as part of a combination with
immunotherapies,” said Gisela Schwab, M.D., President, Product
Development and Medical Affairs and Chief Medical Officer,
Exelixis. “The promising clinical activity observed for these
cohorts in CheckMate 040 suggests combination therapy with
cabozantinib and immunotherapy may potentially benefit patients
with this aggressive disease.”
More information about this trial is available at
ClinicalTrials.gov.
About CheckMate 040
CheckMate 040 is a phase 1/2, open-label trial investigating
nivolumab or nivolumab-based combinations in patients with advanced
HCC with and without chronic viral hepatitis who are naïve,
intolerant to or who have progressed during sorafenib therapy.
Patients in the cabozantinib combination cohort were randomized 1:1
to receive either nivolumab plus cabozantinib or nivolumab plus
cabozantinib and ipilimumab. Primary endpoints include ORR
(investigator assessed using RECIST v1.1) and safety/tolerability.
The trial is sponsored by Bristol-Myers Squibb. Exelixis is
co-funding the trial and providing cabozantinib. Ipsen has opted in
to participate in the trial and is contributing to the funding for
this study under the terms of our collaboration agreement.
About HCC
Liver cancer is a leading cause of cancer death worldwide,
accounting for more than 700,000 deaths and 800,000 new cases each
year.1 In the U.S., the incidence of liver cancer has more than
tripled since 1980.2 HCC is the most common form of liver cancer,
making up about three-fourths of the estimated 43,000 new cases in
the U.S. in 2020.2 HCC is the fastest-rising cause of
cancer-related death in the U.S.3 Without treatment, patients with
advanced HCC usually survive less than 6 months.4
About CABOMETYX® (cabozantinib)
In the U.S., CABOMETYX tablets are approved for the treatment of
patients with advanced RCC and for the treatment of patients with
HCC who have been previously treated with sorafenib. CABOMETYX
tablets have also received regulatory approvals in the European
Union and additional countries and regions worldwide. 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.
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 occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4
hemorrhage. Do not administer CABOMETYX to patients who have a
recent history of hemorrhage, including hemoptysis, hematemesis, or
melena.
- Perforations and Fistulas: Gastrointestinal (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Monitor patients for signs and symptoms of
perforations and fistulas, including abscess and sepsis.
Discontinue CABOMETYX in patients who experience a fistula that
cannot be appropriately managed 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
event requiring medical intervention.
- Hypertension and Hypertensive Crisis: CABOMETYX can
cause hypertension, including hypertensive crisis. Hypertension
occurred in 36% (17% 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. Discontinue CABOMETYX for severe
hypertension that cannot be controlled with anti-hypertensive
therapy or for hypertensive crisis.
- Diarrhea: Diarrhea occurred in 63% of CABOMETYX
patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients.
Withhold CABOMETYX until improvement to Grade 1 and resume at a
reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea
that cannot be managed with standard antidiarrheal treatments, or
Grade 4 diarrhea.
- Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
44% 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.
- Proteinuria: Proteinuria occurred in 7% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. 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 28 days prior to scheduled dental
surgery or invasive dental procedures. Withhold CABOMETYX for
development of ONJ until complete resolution.
- Wound Complications: Wound complications were reported
with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled
surgery. Resume CABOMETYX after surgery based on clinical judgment
of adequate wound healing. Withhold CABOMETYX in patients with
dehiscence or wound healing complications requiring medical
intervention.
- Reversible Posterior Leukoencephalopathy Syndrome
(RPLS): RPLS, a syndrome of subcortical vasogenic edema
diagnosed by characteristic finding 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.
- 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 commonly reported (≥25%)
adverse reactions are: diarrhea, fatigue, decreased appetite, PPE,
nausea, hypertension, and vomiting.
- 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.
- 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. CABOMETYX is not
recommended for use in patients with severe hepatic
impairment.
Please see accompanying full Prescribing Information
https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.
About Exelixis
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 system genetics, 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. Our discovery efforts have resulted in four commercially
available products, CABOMETYX® (cabozantinib), COMETRIQ®
(cabozantinib), COTELLIC® (cobimetinib) and MINNEBRO®
(esaxerenone), and we 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.
Exelixis is a member of 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, follow @ExelixisInc on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statements
This press release contains forward-looking statements,
including, without limitation, statements related to: Exelixis’
expectation that data from the cabozantinib cohort of the CheckMate
040 trial will be presented at the 2020 ASCO GI; the potential for
cabozantinib in combination with immunotherapy to offer a powerful
and attractive new approach in the treatment of advanced HCC; 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: the availability of data at the referenced
times; risks and uncertainties related to regulatory review and
approval processes and Exelixis’ compliance with applicable legal
and regulatory requirements; the potential failure of the
combination of cabozantinib and nivolumab with or without
ipilimumab to demonstrate safety and/or efficacy in future trials;
uncertainties inherent in the product development process; the
costs of conducting clinical trials, including the ability or
willingness of Exelixis’ collaboration partners to invest in the
resources necessary to complete the 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 discussed under the
caption “Risk Factors” in Exelixis’ Quarterly Report on Form 10-Q
filed with the Securities and Exchange Commission (SEC) on October
30, 2019, 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. MINNEBRO is a
Japanese trademark.
Opdivo® and Yervoy® are registered trademarks
of Bristol-Myers Squibb Company.
1 International Agency for Research on Cancer. GLOBOCAN 2018.
Liver Fact Sheet. Available at:
http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf.
Accessed January 2020.
2 American Cancer Society: Cancer Facts & Figures 2020.
Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.
Accessed January 2020.
3 Siegel R, Miller K, Jemal A: Cancer Statistics, 2020. CA: A
Cancer Journal for Clinicians. Volume 70, Issue 1: 7-30. Available
at:
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590.
Accessed January 2020.
4 Weledji E, Orock G, Ngowe M, NsaghaD. How grim is
hepatocellular carcinoma? Ann Med Surg. 2014. 3:71-76.
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version on businesswire.com: https://www.businesswire.com/news/home/20200124005066/en/
Investors: Susan Hubbard EVP, Public Affairs and Investor
Relations Exelixis, Inc. (650) 837-8194 shubbard@exelixis.com
Media: Lindsay Treadway Senior Director, Public Affairs
and Advocacy Relations Exelixis, Inc. (650) 837-7522
ltreadway@exelixis.com
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