– Median overall survival of 13 months in patients with
microsatellite-stable (MSS) disease –
– Durable responses observed in heavily pretreated patient
– Top-line results for IMblaze370, the phase 3 pivotal trial of
the cobimetinib-atezolizumab combination in MSS colorectal cancer are
anticipated in 1H 2018 –
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Jan. 20, 2018--
Inc. (NASDAQ:EXEL) today announced the presentation of updated
results from the Genentech-sponsored phase 1b clinical trial of
cobimetinib (COTELLIC®), an Exelixis-discovered MEK
inhibitor, in combination with atezolizumab (TECENTRIQ®), an
anti-PDL1 antibody discovered and developed by Genentech, a member of
the Roche Group, in patients with metastatic colorectal cancer (CRC).
Johanna Bendell, M.D., Chief Development Officer at the Sarah Cannon
Research Institute/Tennessee Oncology (Nashville, Tennessee), presented
the results (Abstract #560) during an oral abstract session at the 2018
American Society of Clinical Oncology Gastrointestinal Cancers Symposium
this morning in San Francisco.
“The results of this study suggest the combination of cobimetinib and
atezolizumab continues to be associated with encouraging tolerability
and clinical activity in patients with metastatic colorectal cancer,”
said Michael M. Morrissey, Ph.D., President and Chief Executive Officer
of Exelixis. “In addition, the combination demonstrated a median
13-month overall survival as well as durable responses in patients with
microsatellite-stable tumors, which have historically been resistant to
immunotherapy administered on its own. We look forward to the readout of
IMblaze370, the ongoing confirmatory phase 3 pivotal trial evaluating
the combination of cobimetinib and atezolizumab in the third-line
treatment setting, anticipated in the first half of this year.”
The ongoing phase 1b trial (NCT01988896) evaluates the combination of
cobimetinib and atezolizumab in a variety of solid tumors. Following the
selection of a recommended dose in the trial’s dose escalation stage,
expansion cohorts in metastatic CRC, non-small cell lung cancer, and
melanoma began enrolling. The trial’s primary endpoints are the
evaluation of the safety and tolerability of the combination. Secondary
endpoints include investigator-assessed objective response rate (ORR),
progression-free survival (PFS) by RECIST 1.1, and overall survival (OS).
As of the September 4, 2017 data cut-off, a total of 84 patients with
metastatic CRC from both stages of the trial were evaluable for safety
and clinical activity. All patients were previously treated, with 79
percent (n=66) receiving 5+ prior systemic therapies. Microsatellite
instability (MSI) status was locally reported and centrally confirmed by
next-generation sequencing-based scoring; half of the evaluable patients
(n=42) were classified as having microsatellite-stable (MSS) disease, a
form of CRC for which PD1 and PD-L1 inhibitors alone have shown minimal
activity. An additional 11 percent of patients (n=9) were classified as
MSI-low. One patient was MSI-high, while the MSI status of the remaining
32 patients was unknown. The majority of patients (68 percent; n=57) had
KRAS-mutant tumors. The median follow-up across all CRC patients was
17.0 months (range 0.5 to 33.8 months).
Preliminary Clinical Activity. Across all 84 CRC patients, median
OS was 9.8 months, with 6-month and 12-month landmark OS at 65 and 43
percent, respectively. For patients with confirmed MSS disease (n=42),
median OS was 13.0 months, with 6-month and 12-month landmark OS at 71
and 51 percent, respectively. Across all 84 patients, median PFS was 1.9
months, with six-month landmark PFS at 18 percent. For patients with MSS
disease (n=42), median PFS was 2.5 months, with six-month landmark PFS
at 27 percent.
Investigators also conducted a best overall response (BOR) analysis
across all patients, although seven patients had missing or unevaluable
BOR data. The ORR was eight percent (n=7). Of the seven confirmed
Partial Responses (PRs), four were in patients with MSS tumors, and one
was in a patient with MSI-low tumors. The remaining two PRs were in
patients whose tumor MSI status was unknown. The Disease Control Rate
(PR + Stable Disease [SD]) was 31 percent, comprised of the 7 PRs (8%)
and 19 instances (23%) of SD. The median duration of response was 14.3
Safety. Investigators reported the majority of adverse events
(AEs) were manageable. There were no treatment-related grade 5 AEs, and
the incidence of treatment-related grade 3 and 4 AEs was 38 percent
(n=32). Rash, diarrhea, fatigue, and increased blood creatine
phosphokinase were the most frequent treatment-related grade 3-4 AEs
reported (five percent each).
About the IMblaze370 Phase 3 Pivotal Trial
In early June 2016, shortly before the initial presentation of data from
the phase 1b clinical trial of cobimetinib and atezolizumab at the 2016
ASCO Annual Meeting, Genentech initiated IMblaze370, a phase 3 pivotal
trial of cobimetinib plus atezolizumab and atezolizumab monotherapy
versus regorafenib in patients with previously treated, unresectable,
advanced metastatic CRC. The trial targeted an enrollment of 360
patients who had received at least two prior chemotherapy regimens. The
primary endpoint of IMblaze370 is OS. IMblaze370 completed enrollment in
the first quarter of 2017, and Genentech has guided it expects top-line
results from the trial in the first half of 2018. More information about
IMblaze370 is available at www.clinicaltrials.gov.
About the Cobimetinib Development Collaboration
Exelixis discovered cobimetinib internally and advanced the compound to
investigational new drug (IND) status. In late 2006, Exelixis entered
into a worldwide collaboration agreement with Genentech, under which
Exelixis received initial upfront and milestone payments for signing the
agreement and submitting the IND. Following the determination of the
maximum tolerated dose in phase 1 by Exelixis, Genentech exercised its
option to further develop cobimetinib.
Under the terms of the collaboration, Exelixis is entitled to an initial
equal share of U.S. profits and losses, which will decrease as sales
increase, and shares U.S. commercialization costs. Outside of the United
States, Exelixis is eligible to receive royalties on any sales.
Cobimetinib is now approved in multiple countries, including the U.S.,
European Union, Switzerland, Canada, Australia and Brazil, to treat
specific forms of BRAF mutation-positive unresectable or metastatic
melanoma, in combination with vemurafenib (ZELBORAF®). The
trade name for cobimetinib is COTELLIC®. Cobimetinib is also
the subject of a clinical development program aimed at evaluating its
potential in combination with a variety of investigational and approved
therapies in disease settings including metastatic melanoma,
triple-negative breast cancer and colorectal carcinoma.
Important: If a patient’s healthcare provider prescribes ZELBORAF®
(vemurafenib), the patient should also read the Medication Guide that
comes with ZELBORAF®.
TECENTRIQ® (atezolizumab), COTELLIC® (cobimetinib)
and ZELBORAF® (vemurafenib) are registered trademarks of
Genentech, a member of the Roche Group.
COTELLIC® is a prescription medicine that is used with
the medicine ZELBORAF® to treat a type of skin cancer called
that has spread to other parts of the body or cannot be removed by
that has a certain type of abnormal “BRAF” gene.
A patient’s healthcare provider will perform a test to make sure that
COTELLIC® is right for the patient. It is not known if
COTELLIC® is safe and effective in children under 18
years of age.
Important Safety Information
Before taking COTELLIC®, patients should
tell their healthcare provider about all of their medical conditions,
including if they:
have skin problems or history of skin problems, other than melanoma
have bleeding problems, any medical conditions and/or on any
medications that increase the risk of bleeding
have heart problems
have eye problems
have liver problems
have muscle problems
are pregnant or plan to become pregnant. COTELLIC® can
harm an unborn baby.
Females who are able to become pregnant should use effective birth
control during treatment with COTELLIC®, and for two
weeks after the final dose of COTELLIC®.
Patients should talk to their healthcare provider about birth
control methods that may be right for them.
Patients should tell their healthcare provider right away if they
become pregnant or think they are pregnant during treatment with
are breastfeeding or plan to breastfeed. It is not known if COTELLIC®
passes into breast milk. Patients should not breastfeed during
treatment with COTELLIC® and for two weeks after the final
dose. Patients should talk to their healthcare provider about the best
way to feed their baby during this time.
Patients should tell their healthcare provider about all the
medicines they take, including prescription and over-the-counter
medicines, vitamins and herbal supplements. Certain medicines may affect
the blood levels of COTELLIC®.
Patients should know the medicines they take and keep a list of them to
show their healthcare provider and pharmacist when they get a new
How should patients take COTELLIC®?
Patients should take COTELLIC® exactly as their healthcare
provider tells them. Patients should not change their dose or stop
taking COTELLIC® unless their healthcare provider tells
Patients should take COTELLIC® one time a day for 21 days,
followed by seven days off treatment, to complete a 28-day treatment
Patients can take COTELLIC® with or without food.
If a patient misses a dose of COTELLIC® or vomits after
taking their dose, they should take their next dose as scheduled.
What should patients avoid during treatment with COTELLIC®?
Patients should avoid sunlight during treatment with COTELLIC®.
COTELLIC® can make a patient’s skin sensitive to sunlight.
They may burn more easily and get severe sunburns. To help protect
When a patient goes outside, they should wear clothes that protect
their skin, including their head, face, hands, arms and legs.
They should use lip balm and a broad-spectrum sunscreen with SPF 30 or
What are the possible side effects of COTELLIC®?
COTELLIC® may cause serious side effects,
Risk of new skin cancers. COTELLIC® may cause new
skin cancers (cutaneous squamous cell carcinoma, keratoacanthoma or
basal cell carcinoma).
Patients should check their skin
regularly and tell their healthcare provider right away if they have
any skin changes including:
skin sore or reddish bump that bleeds or does not heal
change in size or color of a mole
A patient’s healthcare provider should check the patient’s skin before
they start taking COTELLIC®, and every two months during
treatment with COTELLIC®. A patient’s healthcare provider may
continue to check the patient’s skin for six months after the patient
stops taking COTELLIC®. A patient’s healthcare provider
should also check for cancers that may not occur on the skin. Patients
should tell their healthcare provider about any new symptoms that
develop during treatment with COTELLIC®.
Bleeding problems. COTELLIC® can cause serious
Patients should call their healthcare provider
and get medical attention right away if they get any signs of
red or black stools (looks like tar)
blood in their urine
cough up or vomit blood
stomach (abdominal) pain
unusual vaginal bleeding
dizziness or weakness
Heart problems. A patient’s healthcare provider should do tests
before and during treatment to check the patient’s heart function.
Patients should tell their healthcare provider if they get any of
these signs and symptoms of heart problems:
persistent coughing or wheezing
shortness of breath
swelling of their ankles and feet
increased heart rate
Severe rash. Patients should tell their healthcare provider
right away if they get any of these symptoms:
a rash that covers a large area of their body
Eye problems. Patients should tell their healthcare provider
right away if they get any of these symptoms:
partly missing vision or loss of vision
any other vision changes
A patient’s healthcare provider should check the patient’s eyes if the
patient notices any of the symptoms above.
Liver problems. A patient’s healthcare provider should do blood
tests to check the patient’s liver function before and during
treatment. Patients should tell their healthcare provider right away
if they get any of these symptoms:
yellowing of their skin or the white of their eyes
dark or brown (tea color) urine
nausea or vomiting
feeling tired or weak
loss of appetite
Muscle problems (rhabdomyolysis). COTELLIC® can
cause muscle problems that can be severe. Treatment with COTELLIC®
may increase the level of an enzyme in the blood called creatine
phosphokinase (CPK) and may be a sign of muscle damage. A patient’s
healthcare provider should do a blood test to check the patient’s
levels of CPK before and during treatment. Patients should tell their
healthcare provider right away if they get any of these symptoms:
muscle aches or pain
muscle spasms and weaknes
dark, reddish urine
Skin sensitivity to sunlight (photosensitivity). Skin
sensitivity to sunlight during treatment with COTELLIC® is
common and can sometimes be severe. Patients should tell their
healthcare provider if they get any of these symptoms:
red, painful, itchy skin that is hot to touch
bumps or tiny papules
thickened, dry, wrinkled skin
See “What should patients avoid during treatment with COTELLIC®?”
for information on protecting the skin during treatment with COTELLIC®.
The most common side effects of COTELLIC®
sunburn or sun sensitivity
A patient’s healthcare provider will take blood tests during
treatment with COTELLIC®. The most common
changes to blood tests include:
increased blood levels of liver enzymes (GGT, ALT or AST)
increased blood level of enzyme from muscle (creatine phosphokinase)
decreased blood level of phosphate, sodium or potassium
increased blood level of liver or bone enzyme (alkaline phosphatase)
decreased blood level of a type of white blood cell (lymphocyte)
Patients should tell their healthcare provider if they have any side
effect that bothers them or that does not go away. These are not all the
possible side effects of COTELLIC®.
Patients should call their doctor for medical advice about side effects.
Patients may report side effects to FDA at (800) FDA-1088 or www.fda.gov/medwatch.
Patients may also report side effects to Genentech at (888) 835-2555.
Please see Full COTELLIC® Prescribing
Information and Patient Information for additional Important Safety
Information at www.cotellic.com.
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
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 the combination of cobimetinib and atezolizumab for
patients with metastatic CRC; the expected timing for top-line results
from IMblaze370 in the first half of 2018; the financial terms of
Exelixis’ collaboration with Genentech and eligibility to receive
royalties on sales; 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 “could,” “expects,” “eligible,”
“commitment,” “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’
dependence on its relationship with Genentech/Roche with respect to
cobimetinib and Exelixis’ ability to maintain its rights under the
collaboration; risks related to the potential failure of cobimetinib to
demonstrate safety and efficacy in clinical testing; risks and
uncertainties related to regulatory review and approval processes; the
availability of data at the referenced time; market acceptance and the
availability of coverage and reimbursement for COTELLIC; Exelixis’
ability to conduct clinical trials of its product candidates sufficient
to achieve a positive completion; 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 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, and COTELLIC are registered U.S.
View source version on businesswire.com: http://www.businesswire.com/news/home/20180120005034/en/
Source: Exelixis, Inc.
EVP, Public Affairs and Investor
Lindsay Treadway, 650-837-7522
Public Affairs and Advocacy Relations