|[May 07, 2014]
Exelixis Announces Presentation of Final Phase 1b Data for Cobimetinib in Combination with Vemurafenib at EADO Congress 2014
SOUTH SAN FRANCISCO, Calif. --(Business Wire)--
Exelixis, Inc. (NASDAQ:EXEL) today announced final results from BRIM7,
an ongoing phase 1b clinical trial conducted by Roche and Genentech,
Exelixis' collaborator and a member of the Roche Group (SIX: RO, ROG;
OTCQX: RHHBY), of the BRAF inhibitor (BRAFi) vemurafenib in combination
with the MEK inhibitor cobimetinib in patients with locally
advanced/unresectable or metastatic melanoma carrying a BRAFV600
mutation. Antoni Ribas, M.D., Ph.D., a professor in the department of
medicine at Jonsson Comprehensive Cancer Center at the University of
California, Los Angeles, presented the data during a plenary session
today at the 10th European Association of Dermato-Oncology
(EADO) Congress. The meeting is taking place from May 7-10, 2014, in
"Building on the previous data from the BRIM7 trial, these final results
provide encouraging signs of clinical activity in BRAFi-naïve patients
with the combination of cobimetinib and vemurafenib," said Michael M.
Morrissey, Ph.D., president and chief executive officer of Exelixis. "We
are pleased with the progress Roche has made in investigating
cobimetinib, an Exelixis-discovered compound, in this patient
population. People with this disease still urgently need improved
treatment options, and we look forward to the top-line data from coBRIM,
the ongoing phase 3 pivotal trial, anticipated later this year."
The phase 1b dose escalation study was designed to evaluate the safety
and tolerability of cobimetinib in combination with vemurafenib. The
dose escalation stage of the trial comprised 10 dosing cohorts of 3-6
patients and evaluated three different dosing schedules of cobimetinib
in combination with twice daily administration of vemurafenib. After the
maximum tolerated dose (MTD) was defined, two dose cohorts were expanded
and additional patients with BRAF-mutated melanoma who were either
BRAFi-naïve or vemurafenib-progressing patients were accrued.
As of October 1st, 2013, 129 patients had been treated, comprising 66
patients who had previously progressed while receiving vemurafenib and
63 patients who were BRAFi-naïve. Of the 63 BRAFi-naïve patients, 43
(68%) were previously untreated and 20 (32%) had been treated with
agents other than a BRAFi. The majority of the patients had Stage IV,
M1c melanoma at the time of enrollment (vemurafenib-progressors 82%,
BRAFi-naïve 70%). The median duration of follow-up in
vemurafenib-progressor and BRAFi-naïve patients was 6.3 and 12.7 months,
The final results of the exploratory secondary endpoints of BRIM7 showed
anti-tumor activity for the combination of cobimetinib and vemurafenib.
In BRAFi-naïve patients (n=63), an 87% confirmed overall response rate
(ORR) was achieved, including 10% complete responses and 78% partial
responses. An additional 10% of patients achieved stable disease. The
majority of tumor responses were observed within the first six weeks
following initiation of treatment. The median progression free survival
(PFS) for BRAFi-naïve patients was 13.7 months. Results for
vemurafenib-progressor patients (n=66) showed a 15% confirmed ORR, 42%
stable disease rate, and median PFS of 2.8 months. The median overall
survival (OS) for BRAFi-naïve patients had not been reached, with a 1
year survival estimate of 83%. For the vemurafeib-progressor patients
the median OS was 8.3 months with an estimated 1 year survival of 32%.
The most common adverse events (AEs) regardless of attribution to study
treatment in the 129 patients treated to date were non-acneiform rash,
diarrhea, fatigue, photosensitivity/sunburn, liver laboratory
abnormalities and nausea. The most common (all Grade; = Grade 3) AEs in
BRAFi-naïve patients were non-acneiform rash (87%; 14%) diarrhea (83%;
8%), fatigue (70%; 10%) photosensitivity/sunburn (67%; 3%), liver
laboratory abnormality (67%, 19%) and nausea (57%; 3%). The most common
(all Grade; = Grade 3) AEs in vemurafenib-progressor patients were
diarrhea (47%; 3%), nausea (33%; 3%), non-acneiform rash (33%; 2%),
fatigue (27%; 2%) and liver laboratory abnormality (33%; 6%). Most
adverse events were mild to moderate in severity. Permanent
discontinuation of vemurafenib, cobimetinib or the combination due to
AEs was infrequent, and occurred in 5% (vemurafenib), 2% (cobimetinib)
and 2% (combination) of the vemurafenib progressing patients and 6%
(vemurafenib), 5% (cobimetinib) and 3% (combination) of the BRAFi-naïve
About the Phase 3 Pivotal Trial coBRIM
coBRIM is the multicenter, randomized, double-blind, placebo-controlled
phase 3 clinical trial evaluating the combination of vemurafenib with
cobimetinib versus vemurafenib in previously untreated BRAFV600
mutation positive patients with unresectable locally advanced or
metastatic melanoma. The trial is fully enrolled and data are expected
to be available in 2014.
Cobimetinib (formerly GDC-0973/XL518) is an inhibitor of MEK, a
serine/threonine kinase that is a component of the RAS/RAF/MEK/ERK
pathway. This pathway mediates signaling downstream of growth factor
receptors, and is prominently activated in a wide variety of human
tumors. In preclinical studies, oral dosing of cobimetinib resulted in
sustained inhibition of MEK in RAS or BRAF mutant tumor models.
Cobimetinib is being developed by Roche and Genentech, a member of the
Roche Group, under a collaboration with Exelixis.
About the Collaboration
Exelixis discovered cobimetinib internally and advanced the compound to
investigational new drug (IND) status. In late 2006, Exelixis entered
into a worldwide co-development agreement with Genentech, under which
Exelixis received initial upfront and milestone payments for signing the
agreement and submitting the IND. Exelixis was responsible for
development of cobimetinib through the end of phase 1, at which point
Genentech exercised its option to further develop the compound.
Exelixis is entitled to an initial equal share of U.S. profits and
losses, which will decrease as sales increase, and will share equally in
the U.S. marketing and commercialization costs. Exelixis is eligible to
receive royalties on net sales of the product outside the United States.
In December 2012, Exelixis announced that it exercised its option to
co-promote cobimetinib in the United States.
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of multiple
receptor tyrosine kinases. Another Exelixis-discovered compound,
cobimetinib, a highly selective inhibitor of MEK, is being evaluated by
Roche and Genentech, Inc. (a member of the Roche Group) in a broad
development program under a collaboration with Exelixis. For more
information, please visit the company's web site at www.exelixis.com.
This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical and therapeutic potential of cobimetinib; anticipated
developments with respect to coBRIM, including the expected availability
of top-line data therefrom; the designs, plans and goals for BRIM7 and
coBRIM; the plan of Genentech and Exelixis to share U.S. profits and
losses for cobimetinib and U.S. marketing and commercialization costs
for cobimetinib; and Exelixis' potential receipt of royalties on net
sales of cobimetinib products outside the United States. Words such as
"provide," "encouraging," "investigating," "look forward,"
"anticipated," "designed," "expected," "available," "entitled," "share,"
"will," "potential," 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.
Exelixis' 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: risks related to the potential failure of cobimetinib to
demonstrate safety and efficacy in clinical testing; the availability of
data at the expected times; the clinical, therapeutic and commercial
value of cobimetinib; Exelixis' dependence on its relationship with
Genentech/Roche and Exelixis' ability to maintain its rights under the
collaboration; the uncertainty of regulatory approval processes; 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 (News - Alert)) on May 1, 2014 and in Exelixis' other 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
Exelixis and the Exelixis logo are registered U.S. trademarks.
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