– Median overall survival of 13 months in
patients with microsatellite-stable (MSS) disease –
– Durable responses observed in heavily
pretreated patient population –
– Top-line results for IMblaze370, the phase
3 pivotal trial of the cobimetinib-atezolizumab combination in MSS
colorectal cancer are anticipated in 1H 2018 –
Exelixis, 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 months.
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® Indication
COTELLIC® is a prescription medicine that is used with the
medicine ZELBORAF® to treat a type of skin cancer called
melanoma:
- that has spread to other parts of the
body or cannot be removed by surgery, and
- 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 COTELLIC®.
- 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 medicine.
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 them to.
- Patients should take COTELLIC® one time
a day for 21 days, followed by seven days off treatment, to
complete a 28-day treatment cycle.
- 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 against
sunburn:
- 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 higher.
What are the possible side effects of
COTELLIC®?
COTELLIC® may cause serious side effects,
including:
- 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:
- new wart
- 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 bleeding problems.Patients should call their
healthcare provider and get medical attention right away if they
get any signs of bleeding, including:
- red or black stools (looks like
tar)
- blood in their urine
- headaches
- 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
- tiredness
- 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
- blisters
- peeling skin
- Eye problems. Patients should
tell their healthcare provider right away if they get any of these
symptoms:
- blurred vision
- partly missing vision or loss of
vision
- see halos
- 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
- sun rash
- skin irritation
- 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®
include:
- diarrhea
- nausea
- fever
- vomiting
- 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.
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 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. trademarks.
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version on businesswire.com: http://www.businesswire.com/news/home/20180120005034/en/
Exelixis, Inc.Investors Contact:Susan Hubbard,
650-837-8194EVP, Public Affairs and Investor
Relationsshubbard@exelixis.comorMedia Contact:Lindsay
Treadway, 650-837-7522Director, Public Affairs and Advocacy
Relationsltreadway@exelixis.com
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