Press Release
Press Release
Exelixis’ Phase 3 CELESTIAL Trial of Cabozantinib Meets Primary Endpoint of Overall Survival in Patients with Advanced Hepatocellular Carcinoma
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– Data to be submitted for presentation at an upcoming medical meeting –
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“We are excited that these positive results from the phase 3 CELESTIAL
trial bring us one step closer to the potential of offering previously
treated patients with this aggressive form of advanced liver cancer a
much-needed new treatment option,” said
In
About the CELESTIAL Study
CELESTIAL is a randomized,
double-blind, placebo-controlled study of cabozantinib in patients with
advanced HCC conducted at more than 100 sites globally in 19 countries.
The trial was designed to enroll 760 patients with advanced HCC who
received prior sorafenib and may have received up to two prior systemic
cancer therapies for HCC and had adequate liver function. Enrollment of
the trial was completed in
The primary endpoint for the trial is OS, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.
Based on available clinical trial data from various published trials conducted in the second-line setting of advanced HCC, the CELESTIAL trial statistics for the primary endpoint of OS assumed a median OS of 8.2 months for the placebo arm. A total of 621 events provide the study with 90 percent power to detect a 32 percent increase in median OS (HR = 0.76) at the final analysis. Two interim analyses were planned and conducted at 50 percent and 75 percent of the planned 621 events.
About HCC
Liver cancer is the third-leading cause of death
worldwide, and hepatocellular carcinoma (HCC) is the most common form,
making up about three-fourths of the nearly 41,000 cases that will be
diagnosed in 2017 in the U.S.1,2 Without treatment, patients
with advanced disease usually survive less than 6 months, and it is
estimated that 29,000 people will die due to liver cancer in the U.S.2,3
Worldwide, nearly 800,000 new cases are diagnosed annually, and the
disease accounts for more than 700,000 deaths each year.4
About CABOMETYX® (cabozantinib)
CABOMETYX
is the tablet formulation of cabozantinib. Its targets include MET, AXL
and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been
shown to inhibit the activity of these receptors, which are involved in
normal cellular function and pathologic processes such as tumor
angiogenesis, invasiveness, metastasis and drug resistance. CABOMETYX is
available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg
orally, once daily.
On
On
CABOMETYX is not indicated for the treatment of advanced HCC.
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 hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-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. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-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: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. 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. Dose modification due to diarrhea occurred in 26% of patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): 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: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.
Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.
Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.
Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.
Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Please see full Prescribing Information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
About
Founded in 1994,
Forward-Looking Statement Disclaimer
This press release
contains forward-looking statements, including, without limitation,
statements related to: Exelixis’ plans to submit an sNDA to the
References:
1. Hepatocellular Carcinoma –
2.
3. Weledji E, Orock G, Ngowe M, NsaghaD. How
grim is hepatocellular carcinoma? Annals of Medicine and Surgery.
2014. (3):71-76.
4. Estimated cancer incidence, mortality and
prevalence worldwide.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171016005409/en/
Source:
Exelixis, Inc.
Investors:
Susan Hubbard,
650-837-8194
EVP, Public Affairs and Investor Relations
shubbard@exelixis.com
or
Media:
Lindsay
Treadway, 650-837-7522
Director, Public Affairs and Advocacy
Relations
ltreadway@exelixis.com