– Four new trial cohorts, including non-small cell lung cancer
(NSCLC) and castration-resistant prostate cancer (CRPC) cohorts, added
to expansion phase of combination trial; anticipated to begin enrolling
in first half of 2018 –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Jan. 4, 2018--
Exelixis,
Inc. (NASDAQ:EXEL) today announced an amendment to the protocol for
the phase 1b trial of cabozantinib in combination with atezolizumab
(TECENTRIQ®) in patients with locally advanced or metastatic
solid tumors. The amendment adds four new expansion cohorts to the
trial, which will now include patients with NSCLC and CRPC, in addition
to previously included patients with renal cell carcinoma (RCC) and
urothelial carcinoma (UC). The primary objective in the expansion stage
of this trial remains to determine the objective response rate in each
cohort.
New expansion cohorts include the following:
-
patients with 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
-
patients with NSCLC without a defined tumor genetic alteration who
have progressed following treatment with an immune checkpoint inhibitor
-
patients with UC who have progressed following treatment with an
immune checkpoint inhibitor
-
patients with CRPC who have previously received enzalutamide and/or
abiraterone acetate and experienced radiographic disease progression
in soft tissue
The original trial protocol included four expansion cohorts, which will
remain in the amended study:
-
patients with RCC with clear cell histology who have not had prior
systemic anticancer therapy
-
patients with UC who have progressed on or after platinum-containing
chemotherapy
-
patients with UC who are ineligible for cisplatin-based chemotherapy
and have not received prior systemic chemotherapy for inoperable,
locally advanced or metastatic disease
-
patients with UC who are eligible for cisplatin-based chemotherapy and
have not received prior systemic chemotherapy for inoperable, locally
advanced or metastatic disease
“Patients with advanced non-small cell lung cancer or
castration-resistant prostate cancer are in need of additional therapies
that can slow disease progression,” said Gisela Schwab, M.D., President,
Product Development and Medical Affairs and Chief Medical Officer,
Exelixis. “We are pleased to announce that this phase 1b trial will now
include additional tumor types, as well as advanced kidney and bladder
cancers. Since clinical and preclinical observations indicate that
cabozantinib may promote an immuno-permissive environment, we believe
that its use in combination with immune checkpoint inhibitors such as
atezolizumab may offer potential synergistic effects for both checkpoint
inhibitor-naïve or previously treated patients.”
This multicenter, phase 1b, open-label study is divided into two parts:
a dose-escalation phase and an expansion cohort phase. The
dose-escalation phase is enrolling up to 36 patients either with
advanced RCC with or without prior systemic therapy or with inoperable,
locally advanced, metastatic or recurrent UC (including renal, pelvis,
ureter, urinary bladder and urethra) after prior platinum-based therapy.
The primary objective is to determine the optimal dose and schedule of
daily oral administration of cabozantinib when given in combination with
atezolizumab to inform the trial’s subsequent expansion stage.
Cabozantinib doses of 40 mg daily and 60 mg daily are being evaluated.
All patients will receive the standard atezolizumab dosing regimen (1200
mg infusion once every 3 weeks).
Once the recommended dose and schedule are determined — anticipated to
occur in the first half of 2018 — the trial will begin to enroll the
eight expansion cohorts. Each expansion cohort will initially enroll
approximately 30 participants, although up to 80 may enroll in the
cohorts of patients with UC or NSCLC who have been previously treated
with an immune checkpoint inhibitor, for a total of up to 340 patients.
More information about 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 in to
participate in the funding of the phase 1b trial in patients with
locally advanced or metastatic UC, RCC, CRPC or NSCLC. They may also
participate in future studies at their choosing and 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. Takeda may also participate in this
and future studies and have access to the results to support potential
future regulatory submissions in their territories, if they opt into
their funding obligations under the respective collaboration agreements.
Exelixis holds the exclusive rights to develop and commercialize
cabozantinib in the United States.
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 (UC).1
Kidney cancer is among the top ten most commonly diagnosed forms of
cancer among both men and women in the U.S., according to the American
Cancer Society’s 2017 statistics.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.2 Approximately 30,000 patients in the U.S. and
68,000 globally require treatment.4
Prostate cancer is the second most common cause of cancer death in men,
behind only skin cancer.5 There is a high survival rate for
patients when prostate cancer is detected early, but once the disease
has spread to other parts of the body the five-year survival rate is
just 28 percent.6 Approximately 3,085,000 men were living
with prostate cancer in the U.S. in 2014,7 and an estimated
160,000 new cases will be diagnosed this year.5
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 2014, an estimated 696,440
people were living with bladder cancer in the U.S.10
About Lung Cancer
Lung cancer is the number one cause of cancer-related deaths worldwide,
leading to 1.6 million deaths annually.11 NSCLC accounts for
80 to 85 percent of all cases of lung cancer.12 Survival
rates for lung cancer vary widely depending on how advanced the disease
is at diagnosis. For those diagnosed at an early stage, more than 55
percent survive for five years, but that number drops to 29 percent if
the disease has spread locally and less than 5 percent if it has spread
to distant locations.13 Unfortunately, nearly 80 percent of
lung cancer cases are diagnosed only after the disease has spread at
least locally.13
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 and Switzerland for the treatment of
advanced RCC in adults who have received prior vascular endothelial
growth factor (VEGF)-targeted therapy. Ipsen also submitted to European
Medicines Agency (EMA) the regulatory dossier for cabozantinib as a
treatment for first-line advanced RCC in the European Union on August
28, 2017; on September 8, 2017, Ipsen announced that the EMA validated
the application.
CABOMETYX is not indicated for the treatment of locally advanced or
metastatic UC, NSCLC or CRPC.
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 them 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
or follow @ExelixisInc on Twitter.
Forward-Looking Statement Disclaimer
This press release contains forward-looking statements, including,
without limitation, statements related to: the clinical and therapeutic
potential of cabozantinib, including that it may promote an
immune-permissive environment; Exelixis belief that cabozantinib’s use
in combination with immune checkpoint inhibitors such as atezolizumab
may offer potential synergistic effects for both checkpoint
inhibitor-naïve or previously pre-treated patients; the timing for
determining the recommended dose and schedule for the phase 1b trial and
for enrollment of the eight expansion cohorts, each anticipated to occur
in the first half of 2018; 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 “may,” “believe,” “anticipated,” “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; the availability of data and planned enrollment
efforts to occur at the referenced time; 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 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; 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; 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 November 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.
Exelixis, the Exelixis logo, CABOMETYX, COMETRIQ and COTELLIC are
registered U.S. trademarks.
____________________________________
1 The University of Arizona Cancer Center. What are
genitourinary cancers? http://uacc.arizona.edu/patients/clinic/gucancer/what-are-gu-cancers.
Accessed December 2017.
2 American Cancer Society.
Cancer Facts & Figures 2017. Atlanta: American Cancer Society; 2017.
3
Jonasch E., Gao J., Rathmell W.K., Renal cell carcinoma. BMJ.
2014; 349:g4797.
4 Decision Resources Report: Renal Cell
Carcinoma. October 2014 (internal data on file).
5
American Cancer Society. Key statistics for prostate cancer. Available
at http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics.
Accessed December 2017.
6 American Cancer Society.
Survival rates for prostate cancer. Available at http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates.
Accessed December 2017.
7 National Cancer Institute.
SEER Stat Fact Sheets: Prostate Cancer. Available at http://seer.cancer.gov/statfacts/html/prost.html.
Accessed December 2017.
8 Hurwitz, M. et al. Urothelial
and Kidney Cancers. Cancer Management. http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.
Accessed December 2017.
9 American Cancer Society.
Bladder Cancer Key Statistics. http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statisticshttp://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
Accessed December 2017.
10 National Cancer Institute.
SEER Stat Fact Sheets: Bladder Cancer. http://seer.cancer.gov/statfacts/html/urinb.html.
Accessed December 2017.
11 Torre L.A. et al. Global
cancer statistics, 2012. CA Cancer J Clin. 2015; 65:87-108.
12
American Cancer Society. What Is Non-Small Cell Lung Cancer? Available
at https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html.
Accessed December 2017.
13 National Cancer Institute.
SEER Stat Fact Sheets: Lung and Bronchus Cancer. https://seer.cancer.gov/statfacts/html/lungb.html.
Accessed December 2017.

View source version on businesswire.com: http://www.businesswire.com/news/home/20180104005321/en/
Source: Exelixis, Inc.
Investors:
Exelixis, Inc.
Susan Hubbard,
650-837-8194
EVP, Public Affairs and Investor Relations
shubbard@exelixis.com
or
Media:
Exelixis,
Inc.
Claire McConnaughey, 650-837-7052
Senior
Manager, Public Affairs
cmcconn@exelixis.com