- CABOSUN overall survival results and
independent radiology review committee analysis of progression-free
survival data to be presented during poster discussion session on
September 10 -
Exelixis, Inc. (NASDAQ:EXEL) today announced that data from
clinical trials of cabozantinib and cobimetinib will be the subject
of 10 presentations at the European Society for Medical Oncology
(ESMO) 2017 Congress in Madrid, September 8 – 12, 2017.
Progression-free survival by independent radiology review and
updated overall survival results from CABOSUN, a randomized phase 2
clinical trial of cabozantinib compared with sunitinib in patients
with previously untreated advanced renal cell carcinoma (RCC), will
be presented as a late-breaking abstract in the Genitourinary
Tumours, Non-Prostate poster discussion session on Sunday,
September 10. Final data from the phase 1 study of cabozantinib in
combination with nivolumab with or without ipilimumab for the
treatment of metastatic urothelial carcinoma and other
genitourinary malignancies will be presented in the Genitourinary
Tumours, Non-Prostate oral presentation session on Saturday,
September 9. Additionally, poster presentations will detail the
evaluation of cabozantinib in RCC and advanced penile squamous cell
carcinoma, and of cobimetinib in combination studies in metastatic
melanoma.
“We look forward to this year’s ESMO Congress where new data
from the CABOSUN trial of cabozantinib in patients with previously
untreated advanced renal cell carcinoma will be presented, as well
as the final analysis from the study exploring cabozantinib in
combination with nivolumab and ipilimumab in genitourinary tumors,
including metastatic urothelial carcinoma,” said Michael M.
Morrissey, Ph.D., President and Chief Executive Officer of
Exelixis. “The slate of data featuring Exelixis-discovered
compounds demonstrates our commitment to advancing our ongoing
clinical research program to help improve care and outcomes for
patients with cancer.”
Cabozantinib to be featured in eight presentations
The full schedule of cabozantinib presentations expected at the
meeting is as follows:
Oral Presentation
[846O] “Final results of a phase I study of cabozantinib
(Cabo) plus nivolumab (Nivo) and CaboNivo plus Ipilimumab (Ipi) in
patients (pts) with metastatic urothelial carcinoma (mUC) and other
genitourinary (GU) malignancies”Dr. Rosa Nadal, Sidney Kimmel
Comprehensive Cancer Center, Johns Hopkins University, Baltimore,
Maryland, USASession: Genitourinary Tumours, Non-ProstateOral
presentation Saturday, September 9, 9:15 – 10:45 a.m. CEST, Madrid
AuditoriumNote: This is a National Cancer Institute Cancer Therapy
Evaluation Program (NCI-CTEP) study.
Poster Discussion
[LBA38] “Progression-free survival (PFS) by independent
review and updated overall survival (OS) results from Alliance
A031203 trial (CABOSUN): cabozantinib versus sunitinib as initial
targeted therapy for patients (pts) with metastatic renal cell
carcinoma (mRCC)”Dr. Toni Choueiri, Lank Center for
Genitourinary Oncology, Dana-Farber Cancer Institute, Boston,
Massachusetts, USASession: Genitourinary Tumours,
Non-ProstatePoster presented Sunday, September 10, 2:45 – 4:15 p.m.
CEST, Cordoba AuditoriumNote: This is an NCI-CTEP study.
Poster Presentations
[872P] “Outcomes based on plasma biomarkers in METEOR, a
randomized phase 3 trial of cabozantinib (C) vs everolimus (E) in
advanced renal cell carcinoma (RCC)”Dr. Thomas Powles, Barts
Cancer Institute, Cancer Research UK Experimental Cancer Medicine
Centre, Queen Mary University of London, Royal Free NHS Trust,
London, EnglandSession: Genitourinary Tumours, Non-ProstatePoster
presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8
[876P] “Efficacy of cabozantinib (C) after PD-1/PD-L1
checkpoint inhibitors in metastatic renal cell carcinoma (mRCC):
the Gustave Roussy experience”Dr. Lisa Derosa, Gustave Roussy
Institute of Oncology, Villejuif, FranceSession: Genitourinary
Tumours, Non-ProstatePoster presented Sunday, September 10, 1:15 –
2:15 p.m. CEST, Hall 8
[891P] “Outcomes of patients with metastatic renal cell
carcinoma (mRCC) who were treated with second-line (2L) vascular
endothelial growth factor receptor tyrosine kinase inhibitors
(VEGFR-TKI) after first-line (1L) immune checkpoint inhibitor (ICI)
therapy”Dr. A.Y. Shah, Department of Genitourinary Medical
Oncology, The University of Texas MD Anderson Cancer Center,
Houston, Texas, USASession: Genitourinary Tumours,
Non-ProstatePoster presented Sunday, September 10, 1:15 – 2:15 p.m.
CEST, Hall 8
[901P] “Safety and efficacy of cabozantinib for metastatic
renal cell carcinoma (mRCC): real world data from an Italian
Expanded Access Program (EAP)”Dr. G. Procopio, Department of
Medical Oncology, Fondazione IRCCS - Istituto Nazionale dei Tumori,
Milan, ItalySession: Genitourinary Tumours, Non-ProstatePoster
presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8
[912P] “Cabozantinib for the treatment of patients with
metastatic variant histology renal cell carcinoma (vhRCC): a
retrospective study”Dr. M.T. Campbell, Department of
Genitourinary Medical Oncology, Division of Cancer Medicine, The
University of Texas MD Anderson Cancer Center, Houston, Texas,
USASession: Genitourinary Tumours, Non-ProstatePoster presented
Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8
[927TiP] “Cabozantinib in patients with advanced penile
squamous cell carcinoma (PSCC): the open-label, single-arm,
single-center, phase 2, CaboPen trial”Dr. A. Necchi,
Experimental Oncology and Molecular Medicine, Fondazione IRCCS
Istituto Nazionale dei Tumori, Milan, ItalySession: Genitourinary
Tumours, Non-ProstatePoster presented Sunday, September 10, 1:15 –
2:15 p.m. CEST, Hall 8
Cobimetinib to be featured in two presentations
Also at the congress, Exelixis’ collaborator Genentech, a member
of the Roche Group, will present data on cobimetinib, an
Exelixis-discovered compound, in metastatic melanoma. The full
schedule of cobimetinib presentations expected at the meeting is as
follows:
Poster Discussion
[1225PD] “Prognostic impact of early complete metabolic
response on FDG-PET, in BRAF V600 mutant metastatic melanoma
patients treated with combination vemurafenib &
cobimetinib”Dr. Wen Xu, Peter MacCallum Cancer Centre,
Melbourne, AustraliaSession: Melanoma and Other Skin TumoursPoster
presented Monday, September 11, 11:00 a.m. – 12:15 p.m. CEST,
Pamplona Auditorium
Poster Presentation
[1241P] “Impact of duration of response (DOR) on overall
survival (OS) in patients with metastatic melanoma treated with
dacarbazine (DTIC), vemurafenib (V), or cobimetinib plus
vemurafenib (C+V): a pooled analysis”Dr. Karl Lewis, University
of Colorado Cancer Center, Aurora, Colorado, USASession: Melanoma
and Other Skin TumoursPoster presented Sunday, September 10, 1:15 –
2:15 p.m. CEST, Hall 8
About the CABOSUN Study
On May 23, 2016, Exelixis announced that CABOSUN met its primary
endpoint, demonstrating a statistically significant and clinically
meaningful improvement in PFS compared with sunitinib in patients
with advanced intermediate- or poor-risk RCC as determined by
investigator assessment. CABOSUN was conducted by The Alliance for
Clinical Trials in Oncology as part of Exelixis’ collaboration with
the NCI-CTEP. These results were first presented by Dr. Toni
Choueiri at the ESMO 2016 Congress, and published in the Journal of
Clinical Oncology (Choueiri, JCO, 2016).1 In June 2017, a blinded
independent radiology review committee confirmed that cabozantinib
provided a clinically meaningful and statistically significant
improvement in the primary efficacy endpoint of
investigator-assessed PFS.
CABOSUN was a randomized, open-label, active-controlled phase 2
trial that enrolled 157 patients with advanced RCC determined to be
intermediate- or poor-risk by the IMDC criteria. Patients were
randomized 1:1 to receive cabozantinib (60 mg once daily) or
sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off).
The primary endpoint was PFS. Secondary endpoints included overall
survival and objective response rate. Eligible patients were
required to have locally advanced or metastatic clear-cell RCC,
ECOG performance status 0-2 and had to be intermediate or poor risk
per the IMDC criteria (Heng, JCO, 2009).2 Prior systemic treatment
for RCC was not permitted.
Please see Important Safety Information below and full U.S.
prescribing information at
https://cabometyx.com/downloads/cabometyxuspi.pdf.
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.3
The American Cancer Society’s 2017 statistics cite kidney cancer
as among the top ten most commonly diagnosed forms of cancer among
both men and women in the U.S.4 Clear cell RCC is the most common
type of kidney cancer in adults.5 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.6 Approximately 30,000 patients in the U.S. and 68,000
globally require treatment, and an estimated 14,000 patients in the
U.S. each year are in need of a first-line treatment for advanced
kidney cancer.7
Urothelial cancers encompass carcinomas of the bladder, ureter
and renal pelvis at a ratio of 50:3:1, respectively.8 Urothelial
carcinoma occurs mainly in older people, with 90 percent of
patients aged 55 or older.9 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.9 In 2013, an estimated
587,426 people were living with bladder cancer in the U.S.10
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 April 25, 2016, the FDA approved CABOMETYX tablets for the
treatment of patients with advanced RCC who have received prior
anti-angiogenic therapy. In February of 2016, Exelixis and Ipsen
jointly announced an exclusive licensing agreement for the
commercialization and further development of cabozantinib
indications outside of the United States, Canada and Japan. This
agreement was amended in December of 2016 to include
commercialization rights for Ipsen in Canada. On September 9, 2016,
the European Commission approved CABOMETYX tablets for the
treatment of advanced RCC in adults who have received prior
vascular endothelial growth factor (VEGF)-targeted therapy in the
European Union, Norway and Iceland. Ipsen has confirmed its intent
to submit the regulatory dossier for cabozantinib as a treatment
for first-line advanced renal cell carcinoma in the European Union
in the third quarter of 2017.
On January 30, 2017, Exelixis and Takeda Pharmaceutical Company
Limited announced an exclusive licensing agreement for the
commercialization and further clinical development of cabozantinib
for all future indications in Japan, including RCC.
CABOMEYX is not indicated for the treatment of previously
untreated advanced RCC.
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 the Cobimetinib and Vemurafenib Combination
Cobimetinib is a reversible inhibitor that blocks the activity
of MEK, a protein kinase that is part of a key pathway (the
RAS-RAF-MEK-ERK pathway) that promotes cell division and survival.
This pathway is frequently activated in human cancers including
melanoma, where mutation of one of its components (BRAF) causes
abnormal activation in about 50% of cases. Tumors with BRAF
mutations may develop resistance and subsequently progress after
treatment with a BRAF inhibitor. About 50% of patients with BRAF
mutation positive melanoma experience a tumor response when treated
with a BRAF inhibitor, however development of resistance and
subsequent tumor progression limits treatment benefit. Clinical and
preclinical analyses indicated that reactivation of the MEK-ERK
pathway may underlie development of resistance to BRAF inhibitors
in many progressing tumors, and that co-treatment with a BRAF and
MEK inhibitor delays the emergence of resistance in the preclinical
setting, providing the rationale for testing the combination of
vemurafenib and cobimetinib in clinical trials. The U.S. Food &
Drug Administration approved cobimetinib for the treatment of
unresectable or metastatic melanoma with a BRAF V600E or V600K
mutation, in combination with vemurafenib, in 2015. Cobimetinib is
also being investigated in combination with several investigational
and approved medicines, including an immunotherapy, in several
tumor types, including non-small cell lung cancer, colorectal
cancer, triple-negative breast cancer and melanoma.
About Exelixis
Exelixis, Inc. (Nasdaq: EXEL) is a biopharmaceutical company
committed to the discovery, development and commercialization of
new medicines to improve care and outcomes for people with cancer.
Since its founding in 1994, three products discovered at Exelixis
have progressed through clinical development, received regulatory
approval, and entered the marketplace. Two are derived from
cabozantinib, an inhibitor of multiple tyrosine kinases including
VEGF, MET, AXL and RET receptors: CABOMETYX® tablets approved for
previously treated advanced renal cell carcinoma and COMETRIQ®
capsules approved for progressive, metastatic medullary thyroid
cancer. The third product, COTELLIC®, is a formulation of
cobimetinib, a reversible inhibitor of MEK, is marketed under a
collaboration with Genentech (a member of the Roche Group), and is
approved as part of a combination regimen to treat advanced
melanoma. Both cabozantinib and cobimetinib have shown potential in
a variety of forms of cancer and are the subjects of broad clinical
development programs. For more information about Exelixis, please
visit www.exelixis.com or follow @ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements,
including, without limitation, statements related to: future data
presentations from clinical trials of cabozantinib and cobimetinib
at ESMO; Exelixis’ commitment to advancing the company’s ongoing
clinical research program to help improve care and outcomes for
patients with cancer; Ipsen’s confirmation of its intent to submit
the regulatory dossier for cabozantinib as a treatment for
first-line advanced RCC in the European Union in the third quarter
of 2017; and the therapeutic potential and continued development of
both cabozantinib and cobimetinib. Words such as “will,” “look
forward,” “commitment,” “intent,” “potential,” 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; Exelixis’ ability to
conduct clinical trials of cabozantinib sufficient to achieve a
positive completion; risks related to the potential failure of
cabozantinib or cobimetinib to demonstrate safety and efficacy in
clinical testing; risks and uncertainties related to regulatory
review and approval processes; Exelixis’ dependence on its
relationship with Ipsen, including, the level of Ipsen’s investment
in the resources necessary to successfully commercialize
cabozantinib in the territories where it is approved; Exelixis’
dependence on its relationship with Genentech with respect to the
development of cobimetinib; Exelixis’ dependence on third-party
vendors; 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’ quarterly report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on May 1, 2017,
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.
References:
1. Choueiri, T.K., et al. Cabozantinib Versus Sunitinib As
Initial Targeted Therapy for Patients With Metastatic Renal Cell
Carcinoma of Poor or Intermediate Risk: The Alliance A031203
CABOSUN Trial. Journal of Clinical Oncology. 2016; 35:6,
591-597.
2. Heng D.Y., Xie W., Regan M.M., et al. Prognostic factors for
overall survival in patients with metastatic renal cell carcinoma
treated with vascular endothelial growth factor-targeted agents:
Results from a large, multicenter study. Journal of Clinical
Oncology. 2009; 27:5794-5799.
3. The University of Arizona Cancer Center. What are
genitourinary cancers?
http://uacc.arizona.edu/patients/clinic/gucancer/what-are-gu-cancers.
Accessed August 2017.
4. American Cancer Society. Cancer Facts & Figures 2017.
Atlanta: American Cancer Society; 2017.
5. Jonasch, E., Gao, J., Rathmell, W., Renal cell carcinoma.
BMJ. 2014; 349:g4797.
6. 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.
7. Decision Resources Report: Renal Cell Carcinoma. October 2014
(internal data on file).
8. Hurwitz, M. et al. Urothelial and Kidney Cancers. Cancer
Management.
http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.
Accessed August 2017.
9. American Cancer Society. Bladder Cancer Key Statistics.
http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
Accessed August 2017.
10. National Cancer Institute. SEER Stat Fact Sheets: Bladder
Cancer. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed
August 2017.
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Investors:Exelixis, Inc., 650-837-8194Susan HubbardEVP,
Public Affairs andInvestor
Relationsshubbard@exelixis.comorMedia:Exelixis, Inc.Lindsay
Treadway, 650-837-7522Director, Public Affairs andAdvocacy
Relationsltreadway@exelixis.com
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