Press Release
Press Release
Exelixis and Ipsen Initiate Phase 3 Pivotal Trial (COSMIC-312) of Cabozantinib in Combination with Atezolizumab versus Sorafenib in Previously Untreated Advanced Hepatocellular Carcinoma
– Clinical trial will also explore single-agent activity of cabozantinib in the first-line setting –
“Liver cancer is the fastest-rising cause of cancer-related death in the
U.S., underscoring the need for new treatment options for this patient
community,” said
COSMIC-312 is a multicenter, randomized, controlled phase 3 pivotal trial that aims to enroll approximately 640 patients at up to 200 sites globally. Patients will be randomized 6:3:1 to one of three arms: cabozantinib (40 mg) and atezolizumab, sorafenib, or cabozantinib (60 mg).
“With more than 800,000 new diagnoses of liver cancer worldwide each
year and a poor prognosis for patients with advanced disease, there is
an urgent need to identify new treatment options,” said
More information about this trial is available at ClinicalTrials.gov.
About HCC
Liver cancer is the second-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 nearly 42,000 new cases in the U.S.
in 2018.2 HCC is the fastest-rising cause of cancer-related
death in the U.S.3 According to the GLOBOCAN data, it is
estimated that across the
About CABOMETYX® (cabozantinib)
CABOMETYX tablets are approved in
CABOMETYX tablets are also approved in: the
CABOMETYX is not indicated for previously untreated advanced HCC.
About Exelixis’ Collaboration with
On
About Exelixis’ Collaboration with Takeda
On
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 have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
- Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
- Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
- Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
- Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
- Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
- Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
- Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
- Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
- Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
- Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
- Hepatic Impairment: In patients with mild to 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
Founded in 1994,
About
Exelixis Forward-Looking Statements
This press release contains forward-looking statements, including,
without limitation, statements related to: the potential of the
combination of cabozantinib and atezolizumab, or of cabozantinib as a
monotherapy, as treatment options for patients with previously untreated
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: 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 atezolizumab, or of cabozantinib as
a monotherapy, to demonstrate safety and/or efficacy in COSMIC-312;
uncertainties inherent in the product development process, including
evolving regulatory requirements, slower than anticipated patient
enrollment or inability to identify a sufficient number of clinical
trial sites; 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; changes in economic and business conditions;
and other factors affecting
Ipsen Forward-Looking Statement
The forward-looking statements, objectives and targets contained herein are based on the Group’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 the Group’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 the Group’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 the Group. 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 product 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. The Group must face or might face competition from generic products 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 the Group may fail to achieve its objectives and be forced to abandon its efforts with regards to a product in which it has invested significant sums. Therefore, the Group cannot be certain that favorable results obtained during pre-clinical 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 product concerned. There can be no guarantees a product will receive the necessary regulatory approvals or that the product 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 health care legislation; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the Group'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 the Group’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The Group also depends on third parties to develop and market some of its products which could potentially generate substantial royalties; these partners could behave in such ways which could cause damage to the Group’s activities and financial results. The Group 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 the Group’s partners could generate lower revenues than expected. Such situations could have a negative impact on the Group’s business, financial position or performance. The Group 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. The Group’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 the Group’s 2017 Registration Document available on its website (www.ipsen.com).
TECENTRIQ® (atezolizumab) is a registered
trademark of Genentech, a member of the
The information stated above was prepared by
1
2
3 Mittal S, El-Serag HB.
Epidemiology of HCC: Consider the Population.
4
5
Weledji E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular
carcinoma? Annals of Medicine and Surgery. 2014. 3:71-76.
View source version on businesswire.com: https://www.businesswire.com/news/home/20181204006141/en/
Source:
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
Investors:
Eugenia Litz
Vice President,
Investor Relations
Ipsen
+44 (0) 1753 627721
eugenia.litz@ipsen.com
Media:
Ian Weatherhead
Vice President,
Corporate External Communications
Ipsen
+44 (0)
1753 627733
ian.weatherhead@ipsen.com