Exelixis and Ipsen Announce Positive Results from Phase 3
CONTACT-02 Pivotal Trial Evaluating Cabozantinib in Combination
with Atezolizumab in Metastatic Castration-Resistant Prostate
Cancer
– 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
ALAMEDA, Calif. & PARIS –
August 21, 2023 – 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 CRPCProstate 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
PRECAUTIONSHemorrhage: 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
ExelixisExelixis 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 IpsenIpsen 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.
Contacts:
Exelixis
Investors Contact: Susan HubbardEVP, Public Affairs and
Investor Relations(650)
837-8194shubbard@exelixis.com
|
Ipsen
Investor Contact: Craig MarksVice President, Investor
Relations+44 7584 349
193craig.marks@ipsen.com |
Exelixis
Media Contact: Claire
McConnaughey Senior Director, Public Affairs
(650) 837-7052
cmcconn@exelixis.com |
Ipsen
Media Contact:Joanna ParishGlobal Head of
Franchise Communications, Oncology+44 7840 023
741 joanna.parish@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
StatementsThe 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 20232 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.
- Ipsen PR_Phase 3 Results CONTACT 02_21082023
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