– Ten new trial cohorts added to expansion
phase of combination trial, bringing the total number of cohorts to
18 –
Exelixis, Inc. (Nasdaq:EXEL) today announced an amendment to the
protocol for COSMIC-021, the phase 1b trial of cabozantinib
(CABOMETYX®) in combination with atezolizumab (TECENTRIQ®) in
patients with locally advanced or metastatic solid tumors to add 10
new expansion cohorts to the trial. The primary objective in the
expansion stage of this trial remains to determine the objective
response rate in each cohort.
The 10 new expansion cohorts will evaluate the combination of
cabozantinib and atezolizumab in patients with:
- non-small cell lung cancer (NSCLC) with
an EGFR mutation who have progressed following treatment with an
EGFR-targeting tyrosine kinase inhibitor for metastatic
disease
- renal cell carcinoma (RCC) with
non-clear cell histology who have not had prior systemic anticancer
therapy for inoperable, locally advanced, recurrent or metastatic
disease
- triple-negative breast cancer who have
progressed following treatment with at least one prior systemic
therapy for inoperable, locally advanced, recurrent or metastatic
disease
- epithelial ovarian cancer who have
platinum-resistant or refractory disease
- endometrial cancer who have progressed
following treatment with at least one prior systemic therapy for
inoperable, locally advanced, recurrent or metastatic disease
- advanced hepatocellular carcinoma (HCC)
who have a Child-Pugh score of A and have not had prior systemic
anticancer therapy for inoperable, locally advanced, recurrent or
metastatic disease
- gastric or gastroesophageal junction
adenocarcinoma who have progressed following treatment with
platinum-containing or fluoropyrimidine-containing chemotherapy for
inoperable locally advanced, recurrent or metastatic disease
- colorectal adenocarcinoma who have
progressed following treatment with systemic chemotherapy that
contained fluoropyrimidine in combination with oxaliplatin or
irinotecan for metastatic disease
- head and neck cancer of squamous cell
histology who have progressed following treatment with
platinum-containing chemotherapy for inoperable locally advanced,
recurrent or metastatic disease
- differentiated thyroid cancer who are
radio-refractory or deemed ineligible for treatment with
iodine-131
“We look forward to expanding this phase 1b COSMIC-021 clinical
trial of cabozantinib in combination with atezolizumab in a number
of additional tumor types, which include patient populations in
significant need of new therapies that may improve response rates,
slow disease progression and improve treatment outcomes,” said
Gisela Schwab, M.D., President, Product Development and Medical
Affairs and Chief Medical Officer, Exelixis. “We look forward to
advancing this trial and to generating data that will inform late
stage trials of cabozantinib in combination with immune checkpoint
inhibitors.”
In January 2018, the protocol was amended to include the
following eight expansion cohorts, which are actively enrolling
patients with:
- RCC with clear cell histology who have
not had prior systemic anticancer therapy
- urothelial carcinoma (UC) who have
progressed on or after platinum-containing chemotherapy
- UC who are ineligible for
cisplatin-based chemotherapy and have not received prior systemic
chemotherapy for inoperable, locally advanced or metastatic
disease
- UC who are eligible for cisplatin-based
chemotherapy and have not received prior systemic chemotherapy for
inoperable, locally advanced or metastatic disease
- advanced non-squamous NSCLC without a
defined tumor genetic alteration (EGFR, ALK, ROS1, or BRAF) who
have not received prior therapy with an immune checkpoint
inhibitor
- NSCLC without a defined tumor genetic
alteration who have progressed following treatment with an immune
checkpoint inhibitor
- UC who have progressed following
treatment with an immune checkpoint inhibitor
- castration-resistant prostate cancer
(CRPC) who have previously received enzalutamide and/or abiraterone
acetate and experienced radiographic disease progression in soft
tissue
The dose-escalation phase of the study determined the optimal
dose of cabozantinib as 40 mg daily when given in combination with
atezolizumab (1200 mg infusion once every 3 weeks). Each expansion
cohort of this multicenter phase 1b, open-label study will
initially enroll approximately 30 patients. Up to 80 may enroll in
the cohorts of patients with UC or NSCLC who have been previously
treated with an immune checkpoint inhibitor, with up to a total of
640 patients in the entire study.
More information about the currently enrolling cohorts in this
trial is available at ClinicalTrials.gov.
TECENTRIQ® (atezolizumab) is a registered trademark of
Genentech, a member of the Roche Group.
About Exelixis’ Collaboration with Ipsen
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. On December 21, 2016, this agreement was
amended to include commercialization rights for Ipsen in Canada.
Ipsen has opted to participate in the funding of the previously
announced COSMIC-021 phase 1b trial cohorts in patients with
locally advanced or metastatic UC, RCC, CRPC and NSCLC. They may
also participate in these expansion trial cohorts and in future
studies at their choosing and, in such cases, would have access to
the results to support potential future regulatory submissions.
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 the COSMIC-021 phase 1b trial, or future studies, Takeda
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.
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, and in the
European Union for previously untreated intermediate- or poor-risk
advanced RCC. On May 29, 2018, Exelixis announced that the U.S.
Food and Drug Administration (FDA) accepted for filing the
company’s supplemental New Drug Application (sNDA) for CABOMETYX
tablets as a treatment for patients with previously treated
advanced HCC. On March 28, 2018, Ipsen announced that the European
Medicines Agency validated its application for a new indication for
cabozantinib as a treatment for previously treated advanced HCC in
the European Union.
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. (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 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.
Exelixis Forward-Looking Statement Disclaimer
This press release contains forward-looking statements,
including, without limitation, statements related to: the clinical
and therapeutic potential of cabozantinib in combination with
atezolizumab in patients with locally advanced or metastatic solid
tumors; the potential for COSMIC-021 to generate data that
will inform late stage trials of cabozantinib in combination with
immune checkpoint inhibitors; the potential for Ipsen’s and
Takeda’s participation in future cabozantinib studies under their
respective collaborations and to have access to the results to
support potential future regulatory submissions in their
territories; Exelixis’ commitment to reinvesting in its business to
maximize the potential of its pipeline, including supplementing its
existing therapeutic assets 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 “look
forward,” “may,” “will,” “commitment,” “potential,” “intend,” 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: Exelixis’ ability and the ability of its
collaborators to conduct clinical trials of cabozantinib and
cobimetinib both alone and in combination with other therapies
sufficient to achieve a positive completion; risks related to the
potential failure of cabozantinib and cobimetinib both alone and in
combination with other therapies, 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 level of
costs associated with Exelixis’ commercialization, research and
development and other activities; competition in the area of
business development activities and the inherent uncertainty of the
drug discovery process; Exelixis’ dependence on its relationships
with its cabozantinib collaboration partners, including, the level
of their investment in the resources necessary to successfully
commercialize partnered products in the territories where they are
approved; market acceptance of CABOMETYX, COMETRIQ, and COTELLIC
and the availability of coverage and reimbursement for these
products; 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, including the potential for competitors to
obtain approval for generic versions of Exelixis’ marketed
products; 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 2, 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.
Exelixis, the Exelixis logo and CABOMETYX are
registered U.S. trademarks.
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version on businesswire.com: https://www.businesswire.com/news/home/20180601005200/en/
Exelixis, Inc.Investors:Susan Hubbard, 650-837-8194EVP,
Public Affairs and Investor
Relationsshubbard@exelixis.comorMedia:Lindsay Treadway,
650-837-7522Senior Director, Public Affairs and Advocacy
Relationsltreadway@exelixis.com
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