– Cabozantinib data in a range of tumor types, including advanced hepatocellular carcinoma and advanced renal cell carcinoma, to be presented at ASCO –
– Follow-up data from the phase 1 trial of cabozantinib in combination with nivolumab with or without ipilimumab in metastatic genitourinary cancers to be highlighted –
Exelixis, Inc. EXEL today announced that data from clinical trials of cabozantinib will be the subject of 15 presentations at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting in Chicago, June 1-5, 2018.
Poster presentations will include detailed subset results from the CELESTIAL phase 3 pivotal trial in advanced hepatocellular carcinoma (HCC) comparing outcomes by age and in patients whose only prior treatment was sorafenib. CELESTIAL was the basis for Exelixis' supplemental New Drug Application filed with the U.S. Food and Drug Administration for CABOMETYX® (cabozantinib) tablets as a treatment for patients with previously treated advanced HCC. Additionally, longer follow-up data from the phase 1 trial of cabozantinib in combination with nivolumab with or without ipilimumab in patients with metastatic genitourinary cancers will be featured, along with preliminary safety and efficacy data on cabozantinib plus nivolumab in patients with metastatic urothelial carcinoma refractory to checkpoint inhibitor therapy.
"We're excited about the potential of cabozantinib, both alone and in combination with other therapies, across a range of difficult-to-treat cancers and look forward to presenting data from our clinical trials in genitourinary cancers, advanced hepatocellular carcinoma and other tumor types," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "Our data at ASCO underscore our dedication to maximizing results and expanding possibilities for people living with many different cancer types."
Cabozantinib to be featured in 15 presentations
The full
schedule of cabozantinib presentations expected at the meeting is as
follows:
Poster Discussion
[Abstract 4019] "Cabozantinib (C) versus Placebo (P) in Patients
(pts) with Advanced Hepatocellular Carcinoma (HCC) who have Received
Prior Sorafenib: Results from the Randomized Phase 3 CELESTIAL Trial"
Ghassan
K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center
Session:
Gastrointestinal (Noncolorectal) Cancer
Poster presented Sunday,
June 3, 8:00 – 11:30 a.m., CDT, Hall A
Discussed at the Poster
Discussion Session on Sunday, June 3, 4:45 – 6:00 p.m., CDT, Hall D2
Poster Presentations
[Abstract 4528] "Clinical Efficacy Of Cabozantinib Plus Nivolumab
(CaboNivo) and CaboNivo Plus Ipilimumab (CaboNivoIpi) in Patients (pts)
with Chemotherapy-refractory Metastatic Urothelial Carcinoma (mUC)
either Naïve (n) or Refractory (r) to Checkpoint Inhibitor (CPI)"
Rosa
Maria Nadal, M.D., M.D., Ph.D., National Cancer Institute, National
Institutes of Health
Session: Genitourinary (Nonprostate) Cancer
Poster
presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract 4556] "Quality-Adjusted Time without Symptoms or Toxicity
(Q-TWiST): Analysis of Cabozantinib (Cabo) vs Sunitinib (Sun) in
Patients with Advanced Renal Cell Carcinoma (aRCC) of Intermediate or
Poor Risk (Alliance A031203)"
Ronald C. Chen, M.D., MPH,
University of North Carolina at Chapel Hill
Session: Genitourinary
(Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 –
11:30 a.m. CDT, Hall A
[Abstract 4579] "Cabozantinib (Cabo) in Advanced Non-clear Cell Renal
Cell Carcinoma (nccRCC): A Retrospective Multicenter Analysis"
Nieves
Martinez Chanza, Dana-Farber Cancer Institute
Session:
Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June
2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract TPS4593] "A Phase I-II Study to Evaluate Safety and
Efficacy of the Combination of Niraparib plus Cabozantinib in Patients
with Advanced Kidney/Urothelial Carcinoma"
Daniel E.
Castellano, M.D., Hospital 12 de Octubre
Session: Genitourinary
(Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 –
11:30 a.m. CDT, Hall A
[Abstract TPS4598] "A Phase 3, Randomized, Open-Label Study of
Nivolumab Combined with Cabozantinib vs Sunitinib in Patients with
Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (RCC;
CheckMate 9ER)"
Toni K. Choueiri, M.D., Dana-Farber Cancer
Institute
Session: Genitourinary (Nonprostate) Cancer
Poster
presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract TPS4601] "CANTATA: A Randomized Phase 2 Study of CB-839 in
Combination with Cabozantinib vs. Placebo with Cabozantinib in Patients
with Advanced/Metastatic Renal Cell Carcinoma"
Nizar M. Tannir,
M.D., FACP, The University of Texas MD Anderson Cancer Center
Session:
Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June
2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract TPS4603] "CABOPRE: Phase II Study of Cabozantinib Prior to
Cytoreductive Nephrectomy (CN) in Locally Advanced and/or Metastatic
Renal Cell Carcinoma (mRCC)"
Guillermo de Velasco, M.D., Ph.D.,
Department of Medical Oncology, University Hospital 12 de Octubre, i +
12, Madrid, Spain
Session: Genitourinary (Nonprostate) Cancer
Poster
presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract 1026] "A Phase II Study of Cabozantinib (Cabo) Alone or in
Combination with Trastuzumab (T) in Patients (pts) with Breast Cancer
Brain Metastases (BCBM)"
Jose Pablo Leone, M.D., Dana-Farber
Cancer Institute
Session: Breast Cancer – Metastatic
Poster
presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A
[Abstract TPS1119] "A Phase II Study of Nivolumab in Combination with
Cabozantinib for Metastatic Triple-Negative Breast Cancer (mTNBC)"
Romualdo
Barroso-Sousa, M.D., Ph.D., Dana-Farber Cancer Institute
Session:
Breast Cancer – Metastatic
Poster presented Saturday, June 2, 8:00
– 11:30 a.m. CDT, Hall A
[Abstract 6088] "A Phase II Trial of Cabozantinib (CABO) for the
Treatment of Radioiodine (RAI)-Refractory Differentiated Thyroid
Carcinoma (DTC) in the First-line Setting"
Marcia S. Brose,
M.D., Ph.D., Department of Otorhinolaryngology, Head and Neck Surgery
and the Abramson Cancer Center of the University of Pennsylvania
Session:
Head and Neck Cancer
Poster presented Saturday, June 2, 1:15 – 4:45
p.m. CDT, Hall A
[Abstract 3555] "A Phase I/II Trial of Cabozantinib (C) with or
without Panitumumab (P) in Patients (pts) with RAS Wild-Type (WT)
Metastatic Colorectal Cancer (mCRC): Clinical Outcomes in Pts with MET
Amplification (amp) Detected in Blood"
Jingquan Jia, M.D.,
Ph.D., Duke University Medical Center
Session: Gastrointestinal
(Colorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30
a.m., CDT, Hall A
[Abstract 4088] "Outcomes in Patients (pts) who had Received
Sorafenib (S) as the Only Prior Systemic Therapy in the Phase 3
CELESTIAL Trial of Cabozantinib (C) versus Placebo (P) in Advanced
Hepatocellular Carcinoma (HCC)"
Robin Kate Kelley, M.D.,
University of California San Francisco
Session: Gastrointestinal
(Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 –
11:30 a.m., CDT, Hall A
[Abstract 4090] "Outcomes Based on Age in the Phase 3 CELESTIAL Trial
of Cabozantinib (C) versus Placebo (P) in Patients (pts) with Advanced
Hepatocellular Carcinoma (HCC)"
Lorenza Rimassa, M.D.,
Humanitas Clinical and Research Center
Session: Gastrointestinal
(Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 –
11:30 a.m., CDT, Hall A
[Abstract TPS4157] "A Phase II Trial of Cabozantinib and Erlotinib
for Patients with EGFR and c-MET Co-expressing Metastatic Pancreatic
Adenocarcinoma"
Olumide B. Gbolahan, MBBS, Indiana University
School of Medicine
Session: Gastrointestinal (Noncolorectal) Cancer
Poster
presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A
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 September 2017. Patients were randomized 2:1
to receive 60 mg of cabozantinib once daily or placebo and were
stratified based on etiology of the disease (hepatitis C, hepatitis B or
other), geographic region (Asia versus other regions) and presence of
extrahepatic spread and/or macrovascular invasion (yes or no). No
cross-over was allowed between the study arms during the blinded
treatment phase of the trial. The primary endpoint for the trial is
overall survival, and secondary endpoints include objective response
rate and progression-free survival. Exploratory endpoints include
patient-reported outcomes, biomarkers and safety.
About Genitourinary Cancers
Genitourinary cancers are those
that affect the urinary tract, bladder, kidneys, ureter, prostate,
testicles, penis or adrenal glands — parts of the body involved in
reproduction and excretion — and include renal cell carcinoma (RCC) and
urothelial carcinoma.1
The American Cancer Society's 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.4 Approximately 30,000 patients in the U.S. and 70,000 globally require treatment.5
Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.6 Urothelial carcinoma occurs mainly in older people; 90 percent of patients with bladder cancer are 55 years or older.7 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.7,8 In 2015, an estimated 708,000 people were living with bladder cancer in the U.S.8
About HCC
Liver cancer is the second-leading cause of cancer
death worldwide, accounting for more than 700,000 deaths and nearly
800,000 new cases each year.9 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. HCC is the
fastest-rising cause of cancer-related death in U.S.10
Without treatment, patients with advanced HCC usually survive less than
6 months.11
About CABOMETYX® (cabozantinib)
CABOMETYX
tablets are approved in the United States for the treatment of patients
with advanced RCC. CABOMETYX tablets are also approved in the European
Union, Norway, Iceland, Australia, Switzerland and South Korea for the
treatment of advanced RCC in adults who have received prior
VEGF-targeted therapy. Ipsen also submitted to the EMA the regulatory
dossier for cabozantinib as a treatment for first-line advanced RCC in
the European Union on August 28, 2017; on March 23, 2018, the CHMP
provided a positive opinion for CABOMETYX for the first-line treatment
of intermediate- or poor-risk advanced RCC. 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, including RCC.
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 Exelixis
Founded in 1994, Exelixis, Inc. 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 genetic systems, 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. We discovered our lead compounds cabozantinib and
cobimetinib, and advanced them into clinical development before entering
into partnerships with leading biopharmaceutical companies in our
efforts to bring these medicines to patients globally. We are steadfast
in our commitment to prudently reinvest in our business to maximize the
potential of our pipeline. We intend to supplement 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
recently earned a spot on Deloitte's Technology Fast 500 list, a yearly
award program honoring the 500 fastest-growing companies over the past
four years. For more information about Exelixis, please visit www.exelixis.com,
follow @ExelixisInc
on Twitter or like Exelixis,
Inc. on Facebook.
Forward-Looking Statement Disclaimer
This press release
contains forward-looking statements, including, without limitation,
statements related to: the planned presentation of data at the upcoming
2018 Annual Meeting of the American Society of Clinical Oncology (ASCO)
in Chicago, June 1 – 5, 2018; the potential of cabozantinib, both alone
and in combination with other therapies, to treat a range of
difficult-to-treat cancers; 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;
and Exelixis' mission to deliver the next generation of Exelixis
medicines and help patients recover stronger and live longer. Words such
as "will," "continued," "focus," "possibilities," "potential," "intend,"
"expected," "future," or other similar expressions identify
forward-looking statements, but the absence of these words does not
necessarily mean that a statement is not forward-looking. In addition,
any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements. These forward-looking statements 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; the clinical, therapeutic
and commercial potential of cabozantinib; risks related to the potential
failure of cabozantinib to demonstrate safety and efficacy in clinical
testing; Exelixis' ability and the ability of its collaborators to
conduct clinical trials of cabozantinib, both alone and in combination
with other therapies, sufficient to achieve a positive completion;
Exelixis' reliance upon clinical investigators; Exelixis' dependence on
its relationships with its collaboration partners, including, the level
of their investment in the resources necessary to successfully
commercialize partnered compounds in the territories where they are
approved; market acceptance of CABOMETYX, COMETRIQ, and COTELLIC and the
availability of coverage and reimbursement for these products; the level
of costs associated with Exelixis' commercialization, research and
development, in-licensing or acquisition of product candidates, and
other activities; Exelixis' dependence on third-party vendors for the
development, manufacture and supply of its products; Exelixis' ability
to protect the company's intellectual property rights; market
competition; changes in economic and business conditions, and other
factors discussed under the caption "Risk Factors" in Exelixis' annual
report on Form 10-K filed with the Securities and Exchange Commission
(SEC) on February 26, 2018, and in Exelixis' future filings with the
SEC. The forward-looking statements made in this press release speak
only as of the date of this press release. Exelixis expressly disclaims
any duty, obligation or undertaking to release publicly any updates or
revisions to any forward-looking statements contained herein to reflect
any change in Exelixis' expectations with regard thereto or any change
in events, conditions or circumstances on which any such statements are
based.
# # #
1 The University of Arizona Cancer Center. What are
genitourinary cancers? http://uacc.arizona.edu/patients/clinic/gucancer/what-are-gu-cancers.
Accessed April 2018.
2 American Cancer
Society: Cancer Facts and Figures 2018. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf.
Accessed April 2018.
3 Jonasch, E., Gao, J.,
Rathmell, W., Renal cell carcinoma. BMJ. 2014; 349:g4797.
4
Ko, J., Choueiri, T., et al. First-, second- third-line therapy for
mRCC: benchmarks for trial design from the IMDC. British Journal of
Cancer. 2014; 110:1917-1922.
5 Decision
Resources Report: Renal Cell Carcinoma. October 2014 (internal data on
file).
6 Hurwitz, M. et al. Urothelial and
Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.
Accessed April 2018.
7 American Cancer
Society. Bladder Cancer Key Statistics. http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
Accessed April 2018.
8 National Cancer
Institute. SEER Stat Fact Sheets: Bladder Cancer. http://seer.cancer.gov/statfacts/html/urinb.html.
Accessed April 2018.
9 Cancer Incidence and
Mortality Worldwide. Liver Cancer. International Agency for Research on
Cancer, GLOBOCAN 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed April 2018.
10 Mittal S, El-Serag
HB. Epidemiology of HCC: Consider the Population. Journal of Clinical
Gastroenterology. 2013. 47:S2-S6.
11 Weledji
E, Orock G, Ngowe M, NsaghaD. How grim is hepatocellular carcinoma? Annals
of Medicine and Surgery. 2014. 3:71-76.
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