– CONTACT-03 is the third of three phase 3
pivotal trials that are part of a clinical collaboration with Roche
–
Exelixis, Inc. (NASDAQ: EXEL) today announced the initiation of
CONTACT-03, a global phase 3 pivotal trial of cabozantinib
(CABOMETYX®) in combination with atezolizumab (TECENTRIQ®) in
patients with inoperable, locally advanced or metastatic renal cell
carcinoma (RCC) who progressed during or following treatment with
an immune checkpoint inhibitor as the immediate preceding therapy.
CONTACT-03 is part of a clinical trial collaboration between
Exelixis and Roche that includes two additional phase 3 pivotal
trials – CONTACT-01 in patients with metastatic non-small cell lung
cancer (NSCLC) who have been previously treated with an immune
checkpoint inhibitor and platinum-containing chemotherapy and
CONTACT-02 in patients with metastatic castration-resistant
prostate cancer (CRPC) who have been previously treated with one
novel hormonal therapy – both initiated in June 2020.
“The treatment landscape for metastatic kidney cancer is rapidly
evolving as the use of immune checkpoint inhibitor-based regimens
move to earlier lines of therapy,” said Gisela Schwab, M.D.,
President, Product Development and Medical Affairs and Chief
Medical Officer, Exelixis. “More data are needed to better
understand the sequential use of treatments for this patient
community, and we look forward to learning more about the potential
role of the combination of cabozantinib and atezolizumab following
checkpoint inhibitor therapy in this pivotal trial with our partner
Roche.”
CONTACT-03 is a global, multicenter, randomized, phase 3,
open-label study that aims to enroll approximately 500 patients.
Patients will be randomized 1:1 to the experimental arm of
cabozantinib in combination with atezolizumab or the control arm of
cabozantinib alone. The co-primary endpoints of the trial are
progression-free survival per Response Evaluation Criteria in Solid
Tumors (RECIST) v. 1.1 as assessed by independent review and
overall survival. Secondary endpoints include progression-free
survival, objective response rate and duration of response as
assessed by the investigators. The CONTACT-03 trial is sponsored by
Roche and co-funded by Exelixis.
The design of CONTACT-03 was informed by the ongoing COSMIC-021
trial — a phase 1b study of cabozantinib in combination with
atezolizumab in multiple advanced solid tumors including RCC, NSCLC
and CRPC. More information about CONTACT-03 is available at
ClinicalTrials.gov (NCT04338269).
About RCC
The American Cancer Society’s 2020 statistics cite kidney cancer
as among the top ten most commonly diagnosed forms of cancer among
both men and women in the U.S.1 Clear cell RCC is the most common
type of kidney cancer in adults.2 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%.2 Approximately 32,000 patients in the
U.S. and 71,000 worldwide will require systemic treatment for
advanced kidney cancer in 2020.3
About 70% of RCC cases are known as “clear cell” carcinomas,
based on histology.4 The majority of clear cell RCC tumors have
below-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.7,8,9,10 MET and AXL may provide escape
pathways that drive resistance to VEGF receptor inhibitors.6,7
About CABOMETYX® (cabozantinib) In the U.S., CABOMETYX
tablets are approved for the treatment of patients with advanced
RCC and for the treatment of patients with HCC who have been
previously treated with sorafenib. CABOMETYX tablets have also
received regulatory approvals in the European Union and additional
countries and regions worldwide.
CABOMETYX in combination with atezolizumab is not indicated for
metastatic renal cell carcinoma.
About Exelixis’ Collaboration with Ipsen On February 29,
2016, Exelixis and Ipsen jointly announced an exclusive
collaboration agreement for the further development and
commercialization of cabozantinib outside of the United States,
Canada and Japan. On December 21, 2016, this agreement was amended
to include commercialization rights for Ipsen in Canada. Under the
parties’ collaboration agreement, if Ipsen opts to participate in
funding this phase 3 trial, or future studies, it will have access
to the respective study results to support potential future
regulatory submissions in their territory.
About Exelixis’ Collaboration with Takeda On January 30,
2017, Exelixis and Takeda jointly announced an exclusive licensing
agreement for the commercialization and further development of
cabozantinib indications in Japan. Under the parties’ collaboration
agreement, if Takeda opts to participate in funding this phase 3
trial, or future studies, it will have access to the respective
study results to support potential future regulatory submissions in
their territory.
Exelixis holds the exclusive rights to develop and commercialize
cabozantinib in the United States.
Important Safety Information
Warnings and Precautions
Hemorrhage: Severe and fatal hemorrhages occurred with
CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5%
in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX
for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to
patients who have a recent history of hemorrhage, including
hemoptysis, hematemesis, or melena.
Perforations and Fistulas: Gastrointestinal (GI)
perforations, including fatal cases, occurred in 1% of CABOMETYX
patients. Fistulas, including fatal cases, occurred in 1% of
CABOMETYX patients. Monitor patients for signs and symptoms of
perforations and fistulas, including abscess and sepsis.
Discontinue CABOMETYX in patients who experience a Grade 4 fistula
or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of
thrombotic events. Venous thromboembolism occurred in 7% (including
4% pulmonary embolism) and arterial thromboembolism in 2% of
CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX
patients. Discontinue CABOMETYX in patients who develop an acute
myocardial infarction or serious arterial or venous thromboembolic
event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause
hypertension, including hypertensive crisis. Hypertension occurred
in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do
not initiate CABOMETYX in patients with uncontrolled hypertension.
Monitor blood pressure regularly during CABOMETYX treatment.
Withhold CABOMETYX for hypertension that is not adequately
controlled with medical management; when controlled, resume at a
reduced dose. Discontinue CABOMETYX for severe hypertension that
cannot be controlled with anti-hypertensive therapy or for
hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients.
Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold
CABOMETYX until improvement to Grade 1 and resume at a reduced dose
for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be
managed with standard antidiarrheal treatments, or Grade 4
diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in
44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX
patients. Withhold CABOMETYX until improvement to Grade 1 and
resume at a reduced dose for intolerable Grade 2 PPE or Grade 3
PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX
patients. Monitor urine protein regularly during CABOMETYX
treatment. Discontinue CABOMETYX in patients who develop nephrotic
syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of
CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis,
osteitis, bone erosion, tooth or periodontal infection, toothache,
gingival ulceration or erosion, persistent jaw pain, or slow
healing of the mouth or jaw after dental surgery. Perform an oral
examination prior to CABOMETYX initiation and periodically during
treatment. Advise patients regarding good oral hygiene practices.
Withhold CABOMETYX for at least 3 weeks prior to scheduled dental
surgery or invasive dental procedures, if possible. Withhold
CABOMETYX for development of ONJ until complete resolution.
Impaired Wound Healing: Wound complications occurred with
CABOMETYX. Withhold CABOMETYX for at least 3 weeks prior to
elective surgery. Do not administer CABOMETYX for at least 2 weeks
after major surgery and until adequate wound healing is observed.
The safety of resumption of CABOMETYX after resolution of wound
healing complications has not been established.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
RPLS, a syndrome of subcortical vasogenic edema diagnosed by
characteristic findings on MRI, can occur with CABOMETYX. Evaluate
for RPLS in patients 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.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Verify the pregnancy status of females
of reproductive potential prior to initiating CABOMETYX and advise
them to use effective contraception during treatment and for 4
months after the last dose.
Adverse Reactions
The most commonly reported (≥25%) adverse reactions are:
diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension,
and vomiting.
Drug Interactions
Strong CYP3A4 Inhibitors: If coadministration with strong
CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong
CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Avoid St. John’s wort.
USE IN SPECIFIC POPULATIONS
Lactation: Advise women not to breastfeed during
CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with 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.
(NASDAQ: 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 system
genetics, 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. Our
discovery efforts have resulted in four commercially available
products, CABOMETYX® (cabozantinib), COMETRIQ® (cabozantinib),
COTELLIC® (cobimetinib) and MINNEBRO® (esaxerenone), and we have
entered into partnerships with leading pharmaceutical companies to
bring these important medicines to patients worldwide. Supported by
revenues from our marketed products and collaborations, we are
committed to prudently reinvesting in our business to maximize the
potential of our pipeline. We are supplementing 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 is a member of the Standard & Poor’s (S&P)
MidCap 400 index, which measures the performance of profitable
mid-sized companies. For more information about Exelixis, please
visit www.exelixis.com, follow @ExelixisInc on Twitter or like
Exelixis, Inc. on Facebook.
Forward-Looking Statements This press release contains
forward-looking statements, including, without limitation,
statements related to: the potential role of the combination of
cabozantinib and atezolizumab following checkpoint inhibitor
therapy as a treatment for patients with metastatic kidney cancer;
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: the continuing COVID-19 pandemic and its impact
on Exelixis’ research and development operations, including
Exelixis’ ability to initiate new clinical trials and clinical
trial sites, enroll clinical trial patients, conduct trials per
protocol, and conduct drug research and discovery operations and
related activities; complexities and the unpredictability of the
regulatory review and approval processes in the U.S. and elsewhere;
Exelixis’ and Roche’s continuing compliance with applicable legal
and regulatory requirements; the potential failure of the
combination of cabozantinib and atezolizumab to demonstrate safety
and/or efficacy in CONTACT-03; uncertainties inherent in the
product development process; 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, including the potential for competitors to
obtain approval for generic versions of CABOMETYX; changes in
economic and business conditions; and other factors affecting
Exelixis and its development programs discussed under the caption
“Risk Factors” in Exelixis’ Quarterly Report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on May 5, 2020,
and in Exelixis’ future filings with the SEC. All forward-looking
statements in this press release are based on information available
to Exelixis as of the date of this press release, and Exelixis
undertakes no obligation to update or revise any forward-looking
statements contained herein, except as required by law.
Exelixis, the Exelixis logo, CABOMETYX,
COMETRIQ and COTELLIC are registered U.S. trademarks. MINNEBRO is a
Japanese trademark.
TECENTRIQ® (atezolizumab) is a registered
trademark of Genentech, a member of the Roche Group.
1 American Cancer Society: Cancer Facts & Figures 2020.
Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf.
Accessed July 2020. 2 Jonasch, E., Gao, J., Rathmell, W., Renal
cell carcinoma. BMJ. 2014; 349:g4797. 3 Decision Resources Report:
Renal Cell Carcinoma. October 2014 (internal data on file). 4
American Cancer Society: What is Kidney Cancer? Available at:
https://www.cancer.org/cancer/kidney-cancer/about/what-is-kidney-cancer.html.
Accessed July 2020. 5 Harshman, L., and Choueiri, T. Targeting the
hepatocyte growth factor/c-Met signaling pathway in renal cell
carcinoma. Cancer J. 2013; 19:316-323. 6 Rankin, et al. Direct
regulation of GAS6/AXL signaling by HIF promotes renal metastasis
through SRC and MET. Proc Natl Acad Sci USA. 2014; 111:13373-13378.
7 Zhou, L., Liu, X-D., Sun, M., et al. Targeting MET and AXL
overcomes resistance to sunitinib therapy in renal cell carcinoma.
Oncogene. 2016; 35:2687-2697. 8 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. 1999; 19:5902–5912. 9
Takahashi, A., Sasaki, H., Kim, S., et al. Markedly increased
amounts of messenger RNAs for vascular endothelial growth factor
and placenta growth factor in renal cell carcinoma associated with
angiogenesis. Cancer Res. 1994; 54:4233-4237. 10 Nakagawa, M.,
Emoto, A., Hanada, T., Nasu, N., Nomura, Y. Tubulogenesis by
microvascular endothelial cells is mediated by vascular endothelial
growth factor (VEGF) in renal cell carcinoma. Br J Urol. 1997;
79:681-687.
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Investors Contact: Susan Hubbard EVP, Public Affairs and
Investor Relations Exelixis, Inc. (650) 837-8194
shubbard@exelixis.com
Media Contact: Lindsay Treadway Senior Director, Public
Affairs and Advocacy Relations Exelixis, Inc. (650) 837-7522
ltreadway@exelixis.com
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