Exelixis, Inc. (NASDAQ:EXEL) today announced the initiation of
the dose-escalation stage of a phase 1b trial of cabozantinib in
combination with atezolizumab (TECENTRIQ®) in patients with locally
advanced or metastatic urothelial carcinoma (UC) or renal cell
carcinoma (RCC). 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.
“Patients with locally advanced or metastatic urothelial or
renal cell carcinoma are in need of additional therapies that can
slow disease progression,” said Sumanta Kumar Pal, M.D.,
Co-director, Kidney Cancer Program at City of Hope, and Principal
Investigator of the study. “As new investigational and approved
therapies become available, research into their use in combination
with other treatments may be a productive avenue for improving
clinical outcomes in patients with these tumor types. Identifying
the appropriate dose for cabozantinib when paired with the
immunotherapy atezolizumab is the first step in examining this
potential combination therapy.”
This multicenter phase 1b, open-label study is divided in two
parts: a dose-escalation phase and an expansion cohort phase. The
dose-escalation phase will enroll 9 to 36 patients with inoperable,
locally advanced, metastatic or recurrent UC (including renal,
pelvis, ureter, urinary bladder and urethra) after prior
platinum-based therapy or RCC with or without prior systemic
therapy. The starting dose of cabozantinib will be 40 mg daily and
may be increased to 60 mg daily or decreased to 20 mg daily. All
patients will receive the standard atezolizumab dosing regimen
(1200 mg infusion once every 3 weeks).
The secondary objectives of the dose-escalation stage are to
evaluate the plasma pharmacokinetics of daily oral administration
of cabozantinib when given in combination with atezolizumab and to
assess safety of the combination therapy through the evaluation of
incidence and severity of adverse events, including immune-related
adverse events. Exploratory endpoints include the correlation of
clinical outcome with immune cell, tumor cell and blood biomarker
analyses.
Once the recommended dose and schedule are determined, the trial
will enroll four expansion cohorts, each with up to 30 patients,
for a total of up to 120 patients with advanced or metastatic UC or
RCC. The primary objective in the expansion stage of the trial is
to determine the objective response rate in each cohort. The three
UC expansion cohorts will enroll: 1) patients who have progressed
on or after platinum-containing chemotherapy; 2) patients who are
ineligible for cisplatin-based chemotherapy and have not received
prior systemic chemotherapy for inoperable, locally advanced or
metastatic disease; and 3) patients who are eligible for
cisplatin-based chemotherapy and have not received prior systemic
chemotherapy for inoperable, locally advanced or metastatic
disease. The RCC expansion cohort will enroll patients with clear
cell histology who have not had prior systemic anticancer
therapy.
“There is a strong rationale for combining cabozantinib with
immunotherapies, including clinical and preclinical observations
consistent with the ability of cabozantinib to promote an
immuno-permissive environment, which might present an opportunity
for synergistic effects from combination treatment with immune
checkpoint inhibitors and other immuno-oncology agents,” said
Gisela Schwab, M.D., President, Product Development and Medical
Affairs and Chief Medical Officer, Exelixis. “We are excited to
evaluate the combination of cabozantinib plus atezolizumab and look
forward to the determination of a recommended phase 2 dose and to
further examining this combination regimen to treat advanced
cancers.”
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 or RCC.
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 these 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 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.
Cabozantinib is not indicated for the treatment of locally
advanced or metastatic UC.
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 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
MET, AXL and VEGF receptors: CABOMETYX™ tablets approved for
previously treated advanced kidney cancer and COMETRIQ® capsules
approved for progressive, metastatic medullary thyroid cancer. The
third product, COTELLIC®, is a formulation of cobimetinib, a
selective 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 on 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 potential
of the cabozantinib and atezolizumab combination to treat patients
with locally advanced or metastatic UC or RCC; the potential
opportunity for synergistic effects from the combination of
cabozantinib with immune checkpoint inhibitors and other
immune-oncology agents; the potential for Takeda to participate in
the funding of the phase 1b trial and the potential for both Ipsen
and Takeda to participate in future studies under the clinical
collaboration and have access to the results to support potential
future regulatory submissions in their territories; Exelixis'
commitment to the discovery, development and promotion 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
“potential,” “might,” “look forward,” “may,” “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: Exelixis’ ability
and the ability of its collaborators to conduct clinical trials of
cabozantinib in combination with atezolizumab sufficient to achieve
a positive completion; risks related to the potential failure of
the combination of these compounds to demonstrate safety and
efficacy in clinical testing; Exelixis’ dependence on its
collaboration partners, including, the level of their investment in
the resources necessary to successfully develop cabozantinib in
combination with atezolizumab; the complexities and challenges
associated with regulatory review and approval processes; 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 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.
1.
The University of Arizona Cancer Center.
What are genitourinary cancers?
http://uacc.arizona.edu/patients/clinic/gucancer/what-are-gu-cancers.
Accessed June 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 June 2017.
6.
American Cancer Society. Survival rates
for prostate cancer. Available at
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates.
Accessed June 2017.
7.
National Cancer Institute. SEER Stat Fact
Sheets: Prostate Cancer. Available at
http://seer.cancer.gov/statfacts/html/prost.html. Accessed June
2017.
8.
Hurwitz, M. et al. Urothelial and Kidney
Cancers. Cancer Management.
http://www.cancernetwork.com/cancer-management/urothelial-and-kidney-cancers.
Accessed June 2017.
9.
American Cancer Society. Bladder Cancer
Key Statistics.
http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
Accessed June 2017.
10.
National Cancer Institute. SEER Stat Fact
Sheets: Bladder Cancer.
http://seer.cancer.gov/statfacts/html/urinb.html. Accessed June
2017.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170612005273/en/
Investors:Exelixis, Inc.Susan Hubbard, 650-837-8194EVP,
Public Affairs and Investor
Relationsshubbard@exelixis.comorMedia:Exelixis, Inc.Lindsay
Treadway, 650-837-7522Director, Public Affairs and Advocacy
Relationsltreadway@exelixis.com
Exelixis (NASDAQ:EXEL)
Historical Stock Chart
From Mar 2024 to Apr 2024
Exelixis (NASDAQ:EXEL)
Historical Stock Chart
From Apr 2023 to Apr 2024