BOULDER, Colo., Sept. 28, 2015 /PRNewswire/ -- Clinical
trial results from Array BioPharma's (Nasdaq: ARRY)
wholly-owned MEK inhibitor, binimetinib, and BRAF inhibitor,
encorafenib, were presented this weekend at the European Society of
Medical Oncology's (ESMO) annual European Cancer Conference (ECC).
At the meeting, preliminary data were shared from both a Phase 2
combination trial of binimetinib and encorafenib in BRAF-mutant
melanoma patients (LOGIC2) and a Phase 1b/2 combination trial of
binimetinib and ribociclib (Novartis, LEE011), a CDK4/6 inhibitor
in NRAS-mutant melanoma patients.
Array will hold a conference call to discuss these results and
preliminary results from a colorectal cancer trial on Monday, September 28, 2015. Ron Squarer,
Chief Executive Officer, and Victor
Sandor, M.D., Chief Medical Officer, will lead the call.
Conference Call
Information
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Date:
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Monday, September 28,
2015
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Time:
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9:00 a.m. eastern
time
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Toll-Free:
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(844)
464-3927
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Toll:
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(765)
507-2598
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Pass
Code:
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43837177
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Webcast, including
Replay and Conference Call Slides:
http://edge.media-server.com/m/p/ky8z35w4/lan/en
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BRAF-mutant Melanoma Preliminary Results
LOGIC2 is an ongoing 140-patient, two-part study designed to
explore the safety and activity of novel triplet combinations in
BRAF-mutant melanoma. In part 1, patients are treated with
the combination of binimetinib and encorafenib until disease
progression. Based on the results of molecular profiling at
that time, each patient is assigned to one of four arms containing
a triplet combination of binimetinib, encorafenib and a third
targeted therapy. Results from part 1 of the study are
reported separately for patients who have previously received a
BRAF and/or MEK inhibitor versus those who were initially naive to
BRAF and MEK inhibitor treatment.
In part 1, patients are treated with binimetinib 45 mg twice
daily (BID) and encorafenib 450 mg once daily (QD), the same doses
evaluated in the ongoing Phase 3 COLUMBUS trial. In the
BRAF/MEK-naive group (n=40), the interim overall response rate
(confirmed and unconfirmed complete response or partial response)
was 68%, with a 6-month progression-free survival estimate of 79%.
Of note, 96% of patients in this group continued to receive study
treatment as of the data cutoff. Preliminary data from all patients
in the study (n=89) also indicate that the combination of
binimetinib and encorafenib showed good tolerability with a 12%
incidence of pyrexia and little to no rash or photosensitivity.
These results indicate that the combination of binimetinib and
encorafenib show encouraging clinical activity and an emerging
differentiated tolerability profile relative to other MEK/BRAF
inhibitor combinations.
"MEK and BRAF combination therapy is now established as the
optimal molecularly targeted approach for BRAF mutant melanoma
patients," said Reinhard Dummer,
M.D., investigator, University Hospital Zurich. "In this study, the
combination of encorafenib and binimetinib demonstrated robust
clinical activity, consistent with results from other BRAF/MEK
inhibitor combinations, but with a potentially improved and
differentiated safety profile."
NRAS-mutant Melanoma Interim Results
A Phase 1b/2 study of binimetinib in combination with ribociclib
showed promising preliminary antitumor activity in NRAS-mutant
melanoma patients. Results were shared from 45 patients
enrolled in the dose escalation portion of the study, which
included two dosing schedules (28-day or 21-day cycles). For
the 28-day dosing schedule, patients received continuous twice
daily dosing of binimetinib while receiving ribociclib for 21 days
per 28 day cycle. For the 21-day schedule, both agents were
delivered for 14 days of a 21 day cycle.
For patients receiving the combination on a 28-day cycle (n=22),
the Objective Response Rate (ORR, confirmed and unconfirmed
complete or partial responses) was 41%, the Disease Control Rate
(DCR, confirmed and unconfirmed complete or partial responses and
stable disease) was 82% with a median Progression Free Survival
(mPFS) of 6.7 months. Furthermore, the ORR was 56% (n=9) for
patients receiving dose level 1 of the 28-day schedule consisting
of binimetinib 45 mg BID and the lowest dose of ribociclib (200 mg
QD), indicating that robust activity can be achieved with this dose
and schedule. Common treatment-related adverse events
included elevated creatine phosphokinase (CPK), skin and
gastrointestinal events. Investigation of an alternative
21-day schedule is ongoing.
"Among metastatic melanoma patients, the presence of an
NRAS-mutation is a predictor of poor prognosis, and for this
subgroup of patients, there are currently no approved targeted
therapies," said Carla van
Herpen, M.D., Ph.D., Radboud University Medical Center,
Nijmegen, The Netherlands. "Simultaneous inhibition of
MEK and CDK4/6 protein kinases could suppress the activation
of two major signaling pathways associated with
NRAS mutations and may provide additive, or
synergistic, activity versus single-agent therapy."
About Melanoma
Melanoma is the fifth most common cancer among men and the
seventh most common cancer among women in the United States, with almost 74,000 new
cases and nearly 10,000 deaths from the disease projected in 2015.
BRAF and NRAS mutations occur in approximately 40% to 60% and 15%
to 20%, respectively, of patients with melanoma. When melanoma is
diagnosed early, it is generally a curable disease. However, when
it spreads to other parts of the body, it is the deadliest and most
aggressive form of skin cancer. A person with metastatic melanoma
typically has a short life expectancy with
only approximately 15% of patients surviving for five years
following diagnosis of metastatic disease.
About BRAF, MEK, Binimetinib and Encorafenib
Raf and MEK are key protein kinases in the RAS/RAF/MEK/ERK
pathway, which regulates several key cellular activities including
proliferation, differentiation, migration, survival and
angiogenesis. Inappropriate activation of this pathway has been
shown to occur in many cancers, such as non-small cell lung cancer,
melanoma, colorectal and thyroid cancers. Binimetinib is a
small molecule MEK inhibitor and encorafenib is a small molecule
BRAF inhibitor, both of which target key enzymes in this pathway.
Three Phase 3 trials in advanced cancer patients continue to
advance: NRAS-mutant melanoma (NEMO, with binimetinib), low-grade
serous ovarian cancer (MILO, with binimetinib) and BRAF-mutant
melanoma (COLUMBUS, with binimetinib and encorafenib). The NEMO and
COLUMBUS Part 1 studies completed enrollment in April 2015. NRAS-mutant melanoma represents the
first potential indication for binimetinib, with a projected
regulatory filing estimated in the first half of 2016. Array also
projects a regulatory filing of binimetinib in combination with
encorafenib in BRAF melanoma in 2016.
About Array BioPharma
Array BioPharma Inc. is a biopharmaceutical company focused on
the discovery, development and commercialization of targeted small
molecule drugs to treat patients afflicted with cancer. Six
registration studies are currently advancing related to three
cancer drugs. These programs include binimetinib (MEK162 /
wholly-owned), encorafenib (LGX818 / wholly-owned) and selumetinib
(AstraZeneca). For more information on Array, please go to
www.arraybiopharma.com.
Forward-Looking Statement
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, including statements about the timing of the announcement of
the results of clinical trials for our proprietary programs, the
timing of the completion or initiation of further development of or
regulatory filings for our wholly-owned programs, expectations that
events will occur that will result in greater value for Array, the
potential for the results of ongoing preclinical and clinical
trials to support regulatory approval or the marketing success of a
drug candidate, our future plans to progress and develop our
proprietary programs, and our plans to build a late-stage
development company. These statements involve significant risks and
uncertainties, including those discussed in our most recent annual
report filed on Form 10-K, in our quarterly reports filed on Form
10-Q, and in other reports filed by Array with the Securities and
Exchange Commission. Because these statements reflect our current
expectations concerning future events, our actual results could
differ materially from those anticipated in these forward-looking
statements as a result of many factors. These factors include, but
are not limited to, our ability to effectively and timely conduct
clinical trials in light of increasing costs and difficulties in
locating appropriate trial sites and in enrolling patients who meet
the criteria for certain clinical trials; risks associated with our
dependence on third-party service providers to successfully conduct
clinical trials within and outside the
United States; our ability to achieve and maintain
profitability and maintain sufficient cash resources; and our
ability to attract and retain experienced scientists and
management. We are providing this information as of September 28, 2015. We undertake no duty to
update any forward-looking statements to reflect the occurrence of
events or circumstances after the date of such statements or of
anticipated or unanticipated events that alter any assumptions
underlying such statements.
CONTACT:
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Tricia
Haugeto
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(303)
386-1193
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thaugeto@arraybiopharma.com
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SOURCE Array BioPharma