Exelixis Announces Presentation of Cobimetinib Combination Therapy Data

- November 7th, 2016

Exelixis today announced the presentation of new data from clinical trials of cobimetinib in combination with other therapies to treat forms of advanced melanoma.

Exelixis, Inc. (NASDAQ:EXEL) today announced the presentation of new data from clinical trials of cobimetinib in combination with other therapies to treat forms of advanced melanoma. Data from phase 1b trials of cobimetinib in combination with atezolizumab, and with atezolizumab and vemurafenib, respectively, form the basis for two
Genentech-sponsored phase 3 pivotal trials anticipated to start in 2017. Additionally, data from a pooled analysis of the combination of cobimetinib and vemurafenib demonstrate the potential for the combination to deliver lasting clinical benefit.
The data are being presented at the Society for Melanoma Research 2016
Congress, which is being held November 6-9 in Boston. Cobimetinib, a
selective MEK inhibitor discovered by Exelixis and now the subject of a
worldwide collaboration agreement with Genentech, a member of the Roche
Group, is the subject of seven abstracts at the meeting.
“Since its initial regulatory approval last year, cobimetinib has
continued to generate encouraging data with the potential to broaden its
utility as a key component of combination regimens to treat serious
forms of cancer,” said Michael M. Morrissey, Ph.D., President and Chief
Executive Officer of Exelixis. “If confirmed in the pivotal trials
planned to initiate next year, the cobimetinib/atezolizumab and
triple-combination regimens described in data at this year’s Society for
Melanoma Research Congress could become important new therapeutic
options for clinicians treating multiple forms of advanced melanoma.”
Pivotal Trial in BRAF Wild-Type Melanoma Planned Following
Encouraging Phase 1b Data

In a plenary session at the SMR 2016 Congress today, Jeffrey R. Infante,
M.D., Director of the Drug Development Program and Principal
Investigator at Sarah Cannon Research Institute, Nashville, Tennessee
will present results from the metastatic melanoma cohort of a phase 1b
dose escalation trial of cobimetinib and atezolizumab, an anti-PDL1
antibody developed by Genentech, in patients with solid tumors. The
primary objective of the trial is to determine the safety and clinical
activity of the combination, and key eligibility criteria include ECOG
Performance Status of 0 or 1, measurable disease per RECIST, and no
prior anti-PD-1/PDL1 therapy.
As of the July 12, 2016 data cut-off, 22 patients with metastatic
melanoma were evaluable for safety and efficacy, including 20 patients
with non-ocular melanoma (10 each with BRAF wild type and BRAF
V600-mutation positive disease) and two patients with ocular melanoma.
Among the 20 non-ocular melanoma patients, the objective response rate
(ORR) was 45 percent, with 9 partial responses, including 5 in BRAF
wild-type patients. Median duration of response was 14.9 months (12.9,
upper limit not yet reached) across 9 responders, and was not yet
reached for the BRAF wild-type subgroup. Median progression-free
survival (PFS) was 12 months across all non-ocular melanoma patients
(15.7 months in BRAF wild-type and 11.9 months in BRAF mutation-positive
patients). With a median follow-up of 18.9 months, median overall
survival (OS) for the cohort had not been reached.
All patients in the cohort were evaluable for safety. In this phase 1b
study, investigators reported the combination of cobimetinib and
atezolizumab was generally well tolerated. Treatment-related Grade 3-4
adverse events (AEs) occurred in 59 percent of patients, and no
treatment-related grade 5 AEs were reported.
Based on these results, Genentech plans to initiate a phase 3 pivotal
trial of cobimetinib plus atezolizumab versus a PD-1 inhibitor in
patients with previously untreated BRAF wild-type advanced melanoma next
year. More information on the planned study will be posted to www.ClinicalTrials.gov
when available.
Updated Results for Triple Combination of Cobimetinib, Vemurafenib
and Atezolizumab Set Stage for TRILOGY Pivotal Trial

Also in a plenary session today, Ryan Sullivan, M.D., Instructor in
Medicine at Harvard Medical School and Member of the Cancer Immunology
and Melanoma Programs at Dana-Farber Cancer Institute will present
results from the phase 1b trial of cobimetinib, vemurafenib and
atezolizumab in patients with BRAF V600 mutation-positive metastatic
melanoma. The primary objective of the trial is evaluation of the safety
and tolerability of the triple combination, with secondary endpoints
including PFS, OS, ORR, best overall response, and duration of response,
among others.
Patients in the trial receive the triple combination of cobimetinib,
vemurafenib and atezolizumab following a 28-day run-in cycle of
cobimetinib plus vemurafenib. As of the June 15, 2016 data cut-off, 30
patients with previously untreated BRAF V600 mutation-positive advanced
melanoma who received at least one dose of atezolizumab were evaluable
for safety and efficacy. Responses were seen in 24 of 29 patients (83
percent) evaluable for efficacy, including three complete responses and
21 partial responses. Median duration of response and median PFS were
not estimable due to limited follow-up time; the majority of patients
continued to respond at time of data cut-off (median follow-up of 5.6
months).
Investigators reported the triple combination of cobimetinib,
vemurafenib and atezolizumab was generally well tolerated in this
investigational study. Median safety follow-up was 3.9 months (range
0.7-16.8 months). Grade 3-4 AEs were seen in 40 percent of patients that
received the triple combination, and all AEs resolved after appropriate
intervention. No unexpected AEs, grade 5 AEs or atezolizumab-related
serious AEs occurred.
In early 2017, Genentech and Roche plan to initiate TRILOGY
(NCT02908672), a pivotal placebo-controlled phase 3 trial evaluating the
combination of cobimetinib, vemurafenib and atezolizumab compared to
cobimetinib, vemurafenib and placebo. TRILOGY will enroll an estimated
500 patients with previously untreated BRAF V600 mutation-positive
metastatic melanoma. The primary endpoint of TRILOGY is PFS as
determined by the investigator, and secondary endpoints include PFS by
independent review committee, OS, ORR, duration of response, safety and
pharmacokinetics. For more information, visit www.ClinicalTrials.gov.
Efficacy of Long-Term Cobimetinib and Vemurafenib Detailed in Poster
Session

Also at the SMR 2016 Congress, Prof. Grant McArthur, Co-chair of the
Melanoma and Skin Service at Peter MacCallum Cancer Centre (Melbourne,
Victoria, Australia) and colleagues presented a poster demonstrating the
continuing benefit across all patient subgroups of the combination
therapy of cobimetinib and vemurafenib versus vemurafenib monotherapy as
assessed in the coBRIM phase 3 pivotal trial that formed the basis for
the combination’s regulatory approval to treat BRAF V600-mutation
positive advanced melanoma. The percentage of patients alive at three
years was 37.4 percent for cobimetinib and vemurafenib, as compared to
31.1 percent for patients treated with vemurafenib plus placebo. Median
overall survival was 22.5 months for the combination versus 17.4 months
for vemurafenib alone. The safety profile was similar to what was
reported previously, and discontinuation rates due to AEs were below 20
percent.
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. In November 2013,
Exelixis exercised its option to co-promote cobimetinib in the United
States and fields 25 percent of the U.S. sales force, closely
coordinating its efforts with Genentech. Outside of the United States,
Exelixis is eligible to receive royalties on any sales.
Cobimetinib is now approved in multiple countries, including the United
States, European Union, Switzerland, Canada, Australia and Brazil, to
treat specific forms of BRAF mutation-positive unresectable or
metastatic melanoma, in combination with vemurafenib. The trade name for
cobimetinib is COTELLIC®. Further country approvals
are anticipated in 2016 and beyond. 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.
About Advanced Melanoma
Melanoma is less common, but more aggressive and deadlier than other
forms of skin cancer. When melanoma is diagnosed early, it is generally
a curable disease, but most people with advanced melanoma have a poor
prognosis. The American Cancer Society estimates there will be nearly
74,000 new cases of melanoma and 10,000 melanoma deaths this year in the
United States.
In recent years, there have been significant advances in treatment for
advanced melanoma and people with the disease have more options.
However, it continues to be a serious health issue with a high unmet
need and a steadily increasing incidence over the past 30 years.
COTELLIC® Indication
COTELLIC (cobimetinib) is a prescription medicine that is used with the
medicine Zelboraf® (vemurafenib), 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 for the BRAF gene to
make sure that COTELLIC is right for them. It is not known if COTELLIC
is safe and effective in children under 18 years of age.
COTELLIC® Important Safety Information
Patients should avoid sunlight during treatment with COTELLIC and
Zelboraf. COTELLIC and Zelboraf can make a patient’s skin sensitive to
sunlight. They may burn more easily and get severe sunburns. 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.
COTELLIC and Zelboraf may cause serious side effects, including risk of
new skin cancers, risk of other cancers, bleeding problems, heart
problems, allergic reactions, severe rash and other severe skin
reactions, eye problems, changes in the electrical activity of the heart
(QT prolongation), liver problems or liver injury, muscle problems
(rhabdomyolysis), skin sensitivity to sunlight (photosensitivity),
worsening side effects from radiation treatment, and kidney injury.
Patients should tell their doctor if they are pregnant or plan to become
pregnant, as COTELLIC and Zelboraf can harm an unborn baby. Females who
are able to become pregnant should use effective birth control during
treatment with COTELLIC and Zelboraf and for two weeks after the final
dose of COTELLIC or Zelboraf (whichever is taken later).
Patients should not breastfeed during treatment and for two weeks after
the final dose of COTELLIC or Zelboraf (whichever is taken later).
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. Some types of medicines will affect the blood levels of
COTELLIC.
Common side effects of COTELLIC in combination with Zelboraf include
diarrhea, sunburn or sun sensitivity, nausea, fever and vomiting.
COTELLIC and Zelboraf can also cause changes in blood test results.
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 and Zelboraf.
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 both Full COTELLIC Prescribing Information and Patient
Information and Full Zelboraf Prescribing Information and Medication
Guide for additional Important Safety Information at
www.cotellic.com
and
www.zelboraf.com.
About Exelixis
Exelixis, Inc. (Nasdaq:EXEL) is a biopharmaceutical company committed to
the discovery, development and commercialization of new medicines with
the potential to improve care and outcomes for people with cancer. Since
its founding in 1994, three medicines discovered at Exelixis have
progressed through clinical development to receive regulatory approval.
Currently, Exelixis is focused on advancing cabozantinib, an inhibitor
of multiple tyrosine kinases including MET, AXL and VEGF receptors,
which has shown clinical anti-tumor activity in more than 20 forms of
cancer and is the subject of a broad clinical development program. Two
separate formulations of cabozantinib have received regulatory approval
to treat certain forms of kidney and thyroid cancer and are marketed for
those purposes as CABOMETYX™ tablets (U.S. and EU) and COMETRIQ®
capsules (U.S. and EU), respectively. Another Exelixis-discovered
compound, COTELLIC® (cobimetinib), a selective inhibitor of
MEK, has been approved in major territories including the United States
and European Union, and is being evaluated for further potential
indications by Roche and Genentech (a member of the Roche Group) under a
collaboration with Exelixis. 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 for the
combination of cobimetinib and vemurafenib to deliver lasting clinical
benefit; the potential for the cobimetinib/atezolizumab and
triple-combination regimens described in data at this year’s Society for
Melanoma Research Congress to become important new therapeutic options
for clinicians treating multiple forms of advanced melanoma; the
presentation of data from the metastatic melanoma cohort of a phase 1b
dose escalation trial of cobimetinib and atezolizumab; Genentech’s plan
to initiate a phase 3 pivotal trial of cobimetinib plus atezolizumab
versus a PD-1 inhibitor in patients with previously untreated BRAF
wild-type advanced melanoma next year; the presentation of data from the
phase 1b trial of cobimetinib, vemurafenib and atezolizumab in patients
with BRAF V600 mutation-positive metastatic melanoma; Genentech’s and
Roche’s plan to initiate TRILOGY in early 2017 and expectations
regarding the trial’s enrollment; the financial terms of Exelixis’
collaboration for cobimetinib with Genentech, including, the plan to
share U.S. profits and losses for cobimetinib, and Exelixis’ potential
receipt of royalties on sales of cobimetinib products outside the U.S.;
further country approvals of cobimetinib in combination with vemurafenib
to treat BRAF mutation-positive unresectable or metastatic melanoma
anticipated in 2016 and beyond; the potential for cobimetinib in
combination with a variety of investigational and approved therapies in
disease settings, including metastatic melanoma, triple-negative breast
cancer and colorectal carcinoma; estimates regarding new cases of
melanoma and melanoma deaths in the United States; Exelixis’ commitment
to the discovery, development and commercialization 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 “next,” “anticipated,” “potential,”
“could,” “plans,” “expected,” “will,” “eligible,” “estimates,”
“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: the
availability of data at the referenced times; risks related to the
potential failure of cobimetinib to demonstrate safety and efficacy in
clinical testing; Exelixis’ dependence on its relationship with
Genentech/Roche with respect to cobimetinib and ability to maintain its
rights under the collaboration; the degree of market acceptance of and
the availability of coverage and reimbursement for COTELLIC; the risk
that unanticipated developments could adversely affect the
commercialization of COTELLIC; risks related to the potential failure of
cabozantinib to demonstrate safety and efficacy in clinical testing;
market competition; changes in economic and business conditions; and
other factors discussed under the caption “Risk Factors” in Exelixis’
annual report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on November 3, 2016, 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, COMETRIQ and COTELLIC are registered
U.S. trademarks, and CABOMETYX is a U.S. trademark.

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