– Cabozantinib met the primary endpoint of improving
progression-free survival as compared to sunitinib, decreasing the rate
of disease progression or death by 31 percent –
– Objective response rate significantly improved: 46 percent for
cabozantinib versus 18 percent for sunitinib –
– Exelixis to host investor and media webcast from Copenhagen to
discuss the data on Monday, October 10 –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Oct. 10, 2016--
Exelixis, Inc. (NASDAQ:EXEL) today announced detailed results from the
CABOSUN randomized phase 2 trial of cabozantinib in patients with
previously untreated advanced renal cell carcinoma (RCC) with
intermediate- or poor-risk disease per the International Metastatic
Renal Cell Carcinoma Database Consortium (IMDC). Principal investigator
Toni K. Choueiri, M.D. will present detailed data from late-breaking
CABOSUN abstract [#LBA30_PR] today in the Presidential Symposium 3
session, starting at 16:30 CEST (local Copenhagen time) / 10:30 a.m. EDT
/ 7:30 a.m. PDT at the European Society for Medical Oncology (ESMO)
2016, which is being held October 7 – 11, 2016 in Copenhagen.
CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as
part of Exelixis’ collaboration with the National Cancer Institute’s
Cancer Therapy Evaluation Program (NCI-CTEP).
In CABOSUN, with a median follow-up of 20.8 months, cabozantinib
demonstrated a clinically meaningful and statistically significant 31
percent reduction in the rate of disease progression or death [HR 0.69,
95% CI (0.48-0.99), one-sided P=0.012]. The median progression-free
survival (PFS) for cabozantinib was 8.2 months versus 5.6 months for
sunitinib, corresponding to a 2.6 months (46 percent) improvement
favoring cabozantinib over sunitinib. PFS benefits were independent of
IMDC risk group (intermediate or poor risk) and presence or absence of
bone metastases at baseline. The results for sunitinib were in line with
a previously published retrospective analysis of 1,174 intermediate- and
poor-risk RCC patients from the IMDC database, which documented a median
PFS of 5.6 months with a first-line targeted therapy, mainly sunitinib,
in this patient population.1
Objective response rate (ORR) was also significantly improved, at 46
percent (95% CI 34% – 57%) for cabozantinib versus 18 percent (95% CI
10% to 28%) for sunitinib. With a median follow up of 22.8 months,
median overall survival was 30.3 months for cabozantinib versus 21.8
months for sunitinib [HR 0.80, 95% CI (0.50 - 1.26)].
“The results presented today support the potential of cabozantinib to
become a new therapeutic option for previously untreated patients
following their diagnosis with advanced kidney cancer,” said Toni K.
Choueiri, M.D., Director, Lank Center for Genitourinary Oncology,
Dana-Farber Cancer Institute and chair of the CABOSUN study. “Not only
has cabozantinib surpassed sunitinib, the current standard of care, in
progression-free survival and objective response rate, cabozantinib’s
effects on progression-free survival were also consistently favorable
across patient stratification subgroups including IMDC intermediate
versus poor-risk groups and presence or absence of bone metastases.”
“We at the Alliance for Clinical Trials in Oncology are pleased that
CABOSUN has successfully demonstrated that cabozantinib has the
potential to benefit patients with advanced renal cell carcinoma as a
first-line therapy,” said Michael J. Morris, M.D., Associate Member at
Memorial Sloan Kettering Cancer Center, and Chair of the Alliance
Genitourinary Committee. “We are grateful to everyone who has
participated in the trial, especially the physicians, patients and their
Based on these results, Exelixis plans to submit a Supplemental New Drug
Application (sNDA) for cabozantinib as a treatment of first-line
advanced renal cell carcinoma, and is working with the Alliance to
transfer the complete CABOSUN clinical database to Exelixis.
“The past year has seen a tremendous level of progress in the treatment
of kidney cancer, and we are excited to be at the forefront of bringing
these advancements to patients,” said Michael M. Morrissey, Ph.D.,
president and chief executive officer of Exelixis. “Patients in the
first-line setting with either intermediate- or poor-risk disease
progress rapidly with sunitinib, a current standard of care; therefore,
there is a clear need for new options that provide improved clinical
benefit in this difficult to treat patient population. To that end,
based on the CABOSUN results, we are planning to submit a supplemental
New Drug Application in the United States for cabozantinib as a
first-line treatment for advanced renal cell carcinoma.”
CABOSUN enrolled 157 patients with previously untreated advanced RCC:
80.9 percent of patients were intermediate risk per IMDC criteria and
19.1 percent were poor risk, 36.3 percent of patients had bone
metastases, 46 percent of patients had ECOG Performance Status (PS) 0,
41 percent had ECOG PS 1, and 13 percent had ECOG PS 2. All patients
were included in the efficacy analyses that followed the intent-to-treat
principle. Tumor assessments were performed by the investigators
following RECIST criteria. At the time of the analysis of the primary
endpoint of PFS, the median duration of treatment in CABOSUN was 6.9
months with cabozantinib and 2.8 months with sunitinib; 13 patients
continued on cabozantinib treatment versus 2 patients on sunitinib
treatment. Dose reductions occurred for 58 percent and 49 percent of
patients, respectively. Discontinuation rate due to an adverse event was
20 percent with cabozantinib and 21 percent with sunitinib.
One hundred and fifty patients were evaluable for safety. Ninety-nine
percent of patients on both arms experienced at least one adverse event.
The most common all causality grade 3 or 4 adverse events observed in
more than 5 percent of patients were hypertension (28 percent), diarrhea
(10 percent), palmar-plantar erythrodysesthesia (8 percent), and fatigue
(6 percent) in the cabozantinib arm, and hypertension (22 percent),
fatigue (15 percent), diarrhea and thrombocytopenia (both 11 percent),
and oral mucositis (6 percent) in the sunitinib arm. Treatment-related
grade 5 events occurred in three patients in the cabozantinib arm (acute
kidney injury, sepsis and jejunal perforation) and two patients in the
sunitinib arm (sepsis and vascular disorder).
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. CABOSUN is being conducted by
The Alliance for Clinical Trials in Oncology as part of Exelixis’
collaboration with the National Cancer Institute’s Cancer Therapy
Evaluation Program (NCI-CTEP).
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). 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.
Webcast for the Financial Community and Media
Exelixis and its partner Ipsen will jointly host a live webcast today,
Monday, October 10. The webcast will begin at 19:00 CEST (local
Copenhagen time) / 1:00 p.m. EDT / 10:00 a.m. PDT. During the webcast,
Exelixis and Ipsen management and invited guest speakers will review and
provide context of the results from the CABOSUN study, along with the
other data sets on cabozantinib presented at the conference.
To access the webcast link, log onto www.exelixis.com
and proceed to the Event Calendar page under Investors & Media. Please
connect to the company’s website at least 15 minutes prior to the
webcast to ensure adequate time for any software download that may be
required to view the program. To listen to an audio-only version of the
program by phone, please dial 855-299-5224 (domestic) or 631-267-4890
(international/toll dial) and use passcode 234-026-024. An archived
replay of the webcast will be available on the Event Calendar page under
Investors & Media at www.exelixis.com
after the event concludes.
About Advanced Renal Cell Carcinoma
The American Cancer Society’s 2016 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.1
Approximately 30,000 patients in the U.S. and 68,000 globally require
The majority of clear cell RCC tumors have lower than normal levels of a
protein called von Hippel-Lindau, which leads to higher levels of MET,
AXL and VEGF.5,6 These proteins promote tumor angiogenesis
(blood vessel growth), growth, invasiveness and metastasis.7-10
MET and AXL may provide escape pathways that drive resistance to VEGF
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 renal cell carcinoma who have received prior
anti-angiogenic therapy. On September 9, 2016, the European Commission
approved CABOMETYX tablets for the treatment of advanced renal cell
carcinoma in adults who have received prior vascular endothelial growth
factor (VEGF)-targeted therapy in the European Union, Norway and
Iceland. On February 29, 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.
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
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
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
Please see full Prescribing Information at https://cabometyx.com/downloads/cabometyxuspi.pdf.
Exelixis, Inc. (Nasdaq:EXEL) is a biopharmaceutical company committed to
the discovery, development and commercialization of new medicines with
the potential to improve care and outcomes for people with cancer. Since
its founding in 1994, three medicines discovered at Exelixis have
progressed through clinical development to receive regulatory approval.
Currently, Exelixis is focused on advancing cabozantinib, an inhibitor
of multiple tyrosine kinases including MET, AXL and VEGF receptors,
which has shown clinical anti-tumor activity in more than 20 forms of
cancer and is the subject of a broad clinical development program. Two
separate formulations of cabozantinib have received regulatory approval
to treat certain forms of kidney and thyroid cancer and are marketed for
those purposes as CABOMETYX™ tablets (U.S. and EU) and COMETRIQ® capsules
(U.S. and EU), respectively. Another Exelixis-discovered compound,
COTELLIC® (cobimetinib), a selective inhibitor of MEK, has
been approved in major territories including the United States and
European Union, and is being evaluated for further potential indications
by Roche and Genentech (a member of the Roche Group) under a
collaboration with Exelixis. For more information on Exelixis, please
or follow @ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the presentation of detailed
data from CABOSUN at ESMO; the potential of cabozantinib to become a new
therapeutic option for previously untreated patients following their
diagnosis with advanced kidney cancer; the potential of cabozantinib to
benefit patients with advanced RCC as a first-line therapy; Exelixis’
plans to submit a sNDA in the United States for cabozantinib as a
treatment for first-line advanced RCC; Exelixis' commitment to the
discovery, development and commercialization of new medicines with the
potential to improve care and outcomes for people with cancer; Exelixis’
focus on advancing cabozantinib; and the continued development of
cobimetinib. Words such as “will,” “potential,” “plans,” “committed,”
“focused,” 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 and the ability of
its collaborators to conduct clinical trials of cabozantinib sufficient
to achieve a positive completion; risks related to the potential failure
of cabozantinib to demonstrate safety and efficacy in clinical testing;
risks and uncertainties related to regulatory review and approval
processes and Exelixis’ compliance with applicable legal and regulatory
requirements; the degree of market acceptance of CABOMETYX and the
availability of coverage and reimbursement for CABOMETYX; the risk that
unanticipated developments could adversely affect the commercialization
of CABOMETYX; 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/Roche
with respect to cobimetinib and Exelixis’ ability to maintain its rights
under the collaboration; 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 August 3, 2016, 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
Ko, J. J., Choueiri, T.K., et al. First-, second- third-line therapy
for mRCC: benchmarks for trial design from the IMDC. British
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Decision Resources Report: Renal Cell Carcinoma. October 2014
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Harshman, L.C. and Choueiri, T.K., Targeting the hepatocyte growth
factor/c-Met signaling pathway in renal cell carcinoma. Cancer J.
Rankin et al., Direct regulation of GAS6/AXL signaling by HIF promotes
renal metastasis through SRC and MET. Proc Natl Acad Sci U S A.
Zhou L, Liu X-D, Sun M, et al. Targeting MET and AXL overcomes
resistance to sunitinib therapy in renal cell carcinoma. Oncogene.
2015 Sep 14. doi:10.1038/onc.2015.343. [Epub ahead of print].
Koochekpour et al.,The von Hippel-Lindau tumor suppressor gene
inhibits hepatocyte growth factor/scatter factor-induced invasion and
branching morphogenesis in renal carcinoma cells. Mol Cell Biol.
Takahashi A, Sasaki H, Kim SJ, et al. Markedly increased amounts of
messenger RNAs for vascular endothelial growth factor and placenta
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Cancer Res. 1994;54:4233-4237.
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microvascular endothelial cells is mediated by vascular endothelial
growth factor (VEGF) in renal cell carcinoma. Br J Urol.
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Source: Exelixis, Inc.
Investor Relations & Public Affairs
Lindsay Treadway, 650-837-7522
Affairs & Advocacy Relations