– Cabozantinib in combination with atezolizumab
demonstrated a statistically significant reduction in the risk of
disease progression or death compared with a second novel hormonal
therapy in patients with metastatic castration-resistant prostate
cancer –
– A trend toward improvement in overall
survival was observed at first interim analysis –
– Findings will be presented at an upcoming
medical meeting and discussed with health authorities globally
–
Exelixis, Inc. (Nasdaq: EXEL) and Ipsen (Euronext: IPN; ADR:
IPSEY) today announced that the global phase 3 CONTACT-02 pivotal
trial met one of two primary endpoints, demonstrating a
statistically significant improvement in progression-free survival
(PFS) at the primary analysis. CONTACT-02 is evaluating
cabozantinib (CABOMETYX®) in combination with atezolizumab compared
with a second novel hormonal therapy in patients with metastatic
castration-resistant prostate cancer (mCRPC) and measurable soft
tissue disease who have been previously treated with one novel
hormonal therapy. At a prespecified interim analysis for the
primary endpoint of overall survival (OS) that occurred at the same
time as the primary analysis of PFS, a trend toward improvement of
OS was observed; however, the data were immature and did not meet
the threshold for statistical significance. Therefore, the trial
will continue to the next analysis of OS as planned.
The safety profile of the combination of cabozantinib and
atezolizumab was consistent with the known safety profiles for each
single medicine, and no new safety signals were identified with the
combination.
“These positive findings from CONTACT-02 are highly encouraging
given the need for additional, non-cytotoxic or
non-chemotherapeutic treatment options for this patient
population,” said Neeraj Agarwal, M.D., FASCO, Professor and
Presidential Endowed Chair of Cancer Research at Huntsman Cancer
Institute, University of Utah and the global lead investigator of
the trial. “Cabozantinib in combination with atezolizumab
represents a potential new treatment modality for patients with
metastatic castration-resistant prostate cancer, and we look
forward to sharing the full data at a future medical meeting.”
“Patients with metastatic castration-resistant prostate cancer
face a poor prognosis of less than two years, and many who progress
on a novel hormonal therapy are seeking alternative treatment
options to chemotherapy,” said Vicki L. Goodman, M.D., Executive
Vice President, Product Development & Medical Affairs, and
Chief Medical Officer, Exelixis. “We are pleased to report positive
findings from the CONTACT-02 trial, in which cabozantinib in
combination with an immune checkpoint inhibitor has demonstrated an
efficacy benefit in another tumor type with significant unmet need.
We look forward to discussing these findings with the U.S. Food and
Drug Administration and to presenting further details at an
upcoming medical meeting.”
“With prostate cancer confirmed as the second most commonly
occurring cancer in men globally, the need for innovative new
therapies is extensive, especially for those whose cancer has
progressed to the metastatic castration-resistant form,” said
Howard Mayer, Executive Vice President and Head of Research and
Development at Ipsen. “These results represent the first positive
phase 3 data of its kind for a tyrosine kinase inhibitor and
immunotherapy combination in this indication. We will engage with
regulatory authorities on these data and look forward to further
exploring the potential treatment benefit for a patient population
at such a challenging stage of disease.”
About CONTACT-02 CONTACT-02 is a global, multicenter,
randomized, phase 3, open-label study that enrolled 575 patients
who were randomized 1:1 to the experimental arm of cabozantinib in
combination with atezolizumab and the control arm of a second novel
hormonal therapy (either abiraterone and prednisone or
enzalutamide). The study included patients with mCRPC who have
measurable visceral disease or measurable extrapelvic adenopathy
who have been previously treated with one novel hormonal therapy.
The two primary endpoints of the trial are PFS and OS. The
secondary endpoint is objective response rate. The trial is
sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda
Pharmaceutical Company Limited (Takeda). Takeda is conducting the
trial in Japan. More information about CONTACT-02 is available at
ClinicalTrials.gov.
About CRPC Prostate cancer is the second most common
cancer in men and the fourth most common cancer overall globally.1
In 2020, there were more than 1.4 million new cases of prostate
cancer and about 375,300 deaths worldwide.1 Prostate cancer is
considered mCRPC when it has spread beyond the prostate and does
not respond to androgen-suppression therapies, a common treatment
for prostate cancer.2 Men diagnosed with mCRPC often have a poor
prognosis, with an estimated survival of 1-2 years.3
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 over 60 countries outside the
U.S. and Japan, including the European Union. In 2016, Exelixis
granted Ipsen 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 in combination with atezolizumab is not indicated as a
treatment for mCRPC.
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,
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.
EUROPEAN UNION IMPORTANT SAFETY INFORMATION
For detailed recommendations on the use of CABOMETYX in the
European Union, please see the Summary of Product
Characteristics.
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.
About Ipsen Ipsen is a global, mid-sized
biopharmaceutical company focused on transformative medicines in
Oncology, Rare Disease and Neuroscience. With total sales of €3.0bn
in FY 2022, Ipsen sells medicines in over 100 countries. Alongside
its external-innovation strategy, the Company’s research and
development efforts are focused on its innovative and
differentiated technological platforms located in the heart of
leading biotechnological and life-science hubs: Paris-Saclay,
France; Oxford, U.K.; Cambridge, U.S.; Shanghai, China. Ipsen has
around 5,400 colleagues worldwide and is listed in Paris (Euronext:
IPN) and in the U.S. through a Sponsored Level I American
Depositary Receipt program (ADR: IPSEY). For more information,
visit ipsen.com.
Exelixis Forward-Looking Statements This press release
contains forward-looking statements, including, without limitation,
statements related to: the therapeutic potential of the combination
of cabozantinib and atezolizumab to reduce the risk of disease
progression or death for patients with mCRPC who have been
previously treated with one novel hormonal therapy, compared with a
second novel hormonal therapy; Exelixis’ plans to discuss the trial
data from CONTACT-02 with global health authorities, including the
U.S. Food and Drug Administration, and to present detailed findings
at an upcoming medical meeting; 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; the potential failure of cabozantinib in
combination with atezolizumab to demonstrate safety and efficacy in
clinical testing; uncertainties inherent in the product development
process; Exelixis’ dependence on its relationships with its
cabozantinib commercial collaboration partners, including the level
of investment in the resources necessary to successfully
commercialize the combination of cabozantinib and atezolizumab in
the territories where approved; the costs of conducting clinical
trials, including the ability or willingness of Exelixis’ clinical
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 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.
Ipsen Forward-Looking Statements The forward-looking
statements, objectives and targets contained herein are based on
Ipsen’s management strategy, current views and assumptions. Such
statements involve known and unknown risks and uncertainties that
may cause actual results, performance or events to differ
materially from those anticipated herein. All of the above risks
could affect Ipsen’s future ability to achieve its financial
targets, which were set assuming reasonable macroeconomic
conditions based on the information available today. Use of the
words ‘believes’, ‘anticipates’ and ‘expects’ and similar
expressions are intended to identify forward-looking statements,
including Ipsen’s expectations regarding future events, including
regulatory filings and determinations. Moreover, the targets
described in this document were prepared without taking into
account external-growth assumptions and potential future
acquisitions, which may alter these parameters. These objectives
are based on data and assumptions regarded as reasonable by Ipsen.
These targets depend on conditions or facts likely to happen in the
future, and not exclusively on historical data. Actual results may
depart significantly from these targets given the occurrence of
certain risks and uncertainties, notably the fact that a promising
medicine in early development phase or clinical trial may end up
never being launched on the market or reaching its commercial
targets, notably for regulatory or competition reasons. Ipsen must
face or might face competition from generic medicine that might
translate into a loss of market share. Furthermore, the research
and development process involves several stages each of which
involves the substantial risk that Ipsen may fail to achieve its
objectives and be forced to abandon its efforts with regards to a
medicine in which it has invested significant sums. Therefore,
Ipsen cannot be certain that favorable results obtained during
preclinical trials will be confirmed subsequently during clinical
trials, or that the results of clinical trials will be sufficient
to demonstrate the safe and effective nature of the medicine
concerned. There can be no guarantees a medicine will receive the
necessary regulatory approvals or that the medicine will prove to
be commercially successful. If underlying assumptions prove
inaccurate or risks or uncertainties materialize, actual results
may differ materially from those set forth in the forward-looking
statements. Other risks and uncertainties include but are not
limited to, general industry conditions and competition; general
economic factors, including interest rate and currency exchange
rate fluctuations; the impact of pharmaceutical industry regulation
and healthcare legislation; global trends toward healthcare cost
containment; technological advances, new medicine and patents
attained by competitors; challenges inherent in new-medicine
development, including obtaining regulatory approval; Ipsen’s
ability to accurately predict future market conditions;
manufacturing difficulties or delays; financial instability of
international economies and sovereign risk; dependence on the
effectiveness of Ipsen’s patents and other protections for
innovative medicines; and the exposure to litigation, including
patent litigation, and/or regulatory actions. Ipsen also depends on
third parties to develop and market some of its medicines which
could potentially generate substantial royalties; these partners
could behave in such ways which could cause damage to Ipsen’s
activities and financial results. Ipsen cannot be certain that its
partners will fulfil their obligations. It might be unable to
obtain any benefit from those agreements. A default by any of
Ipsen’s partners could generate lower revenues than expected. Such
situations could have a negative impact on Ipsen’s business,
financial position or performance. Ipsen expressly disclaims any
obligation or undertaking to update or revise any forward-looking
statements, targets or estimates contained in this press release to
reflect any change in events, conditions, assumptions or
circumstances on which any such statements are based, unless so
required by applicable law. Ipsen’s business is subject to the risk
factors outlined in its registration documents filed with the
French Autorité des Marchés Financiers. The risks and uncertainties
set out are not exhaustive and the reader is advised to refer to
Ipsen’s latest Universal Registration Document, available on
ipsen.com.
Exelixis, the Exelixis logo and CABOMETYX are
registered U.S. trademarks of Exelixis.
__________________________ 1 Prostate cancer
statistics. World Cancer Research Fund International. Available at:
https://www.wcrf.org/cancer-trends/prostate-cancer-statistics/.
Accessed August 2023 2 Prostate Cancer: Types of Treatment.
Cancer.Net. Available at:
https://www.cancer.net/cancer-types/prostate-cancer/types-treatment.
Accessed August 2023. 3 Moreira, D. M., et al. Predicting Time From
Metastasis to Overall Survival in Castration-Resistant Prostate
Cancer: Results From SEARCH. Clin Genitourin Cancer. 2017; 15:
60–66.e2.
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version on businesswire.com: https://www.businesswire.com/news/home/20230820936777/en/
Exelixis Investors: Susan Hubbard EVP, Public Affairs and
Investor Relations (650) 837-8194 shubbard@exelixis.com
Exelixis Media: Claire McConnaughey Senior Director,
Public Affairs (650) 837-7052 cmcconn@exelixis.com
Ipsen Investors: Craig Marks Vice President, Investor
Relations +44 7584 349 193 craig.marks@ipsen.com
Ipsen Media: Joanna Parish Global Head of Franchise
Communications, Oncology +44 7840 023 741
joanna.parish@ipsen.com
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