BOULDER, Colo., May 9, 2017 /PRNewswire/ -- Array BioPharma
(Nasdaq: ARRY) today announced top-line results from Part 2 of the
Phase 3 COLUMBUS study evaluating binimetinib, a MEK inhibitor, and
encorafenib, a BRAF inhibitor, in patients with BRAF-mutant
advanced, unresectable or metastatic melanoma. The primary
analysis of Part 2 compared progression free survival (PFS) in
patients treated with binimetinib 45mg twice daily plus encorafenib
300mg daily (COMBO300) to patients treated with encorafenib 300mg
daily as a single agent. The median PFS for patients treated
with COMBO300 was 12.9 months compared to 9.2 months for patients
treated with single agent encorafenib, with HR of 0.77 [95% CI
0.61-0.97, p=0.029]. COMBO300 was generally well-tolerated and
reported dose intensity and adverse events were consistent with
COMBO450 results in COLUMBUS Part 1. Part 2 was designed
specifically to assess the contribution of binimetinib to the
combination of binimetinib and encorafenib by reducing the dose of
encorafenib to 300mg in the combination arm to allow for a
comparison of equal doses across arms. Further results from
Part 2 will be presented at a medical meeting during the second
half of 2017.
"The totality of the COLUMBUS results, including estimated
progression free survival, objective response rate, dose intensity
and tolerability of the combination, provide a strong and
consistent theme across multiple endpoints, underscoring the
promise of binimetinib plus encorafenib as an attractive treatment
option for patients diagnosed with BRAF-mutant melanoma,"
said Keith T. Flaherty, M.D.,
Director of the Termeer Center for Targeted Therapy, Massachusetts
General Hospital and Professor of Medicine, Harvard Medical School.
Ron Squarer, Chief Executive Officer at Array BioPharma noted:
"The robust PFS benefit and tolerability observed with binimetinib
plus encorafenib in COLUMBUS Part 2 once again demonstrates the
combination represents a potentially important addition to the
MEK/BRAF treatment landscape for patients with BRAF-mutant
melanoma. The results of Part 2 confirm the contribution of
binimetinib to the combination."
Based on the strength of data from Part 1 and Part 2, Array is
on track to file an NDA for COLUMBUS in June or July 2017.
About the Phase 3 COLUMBUS Study
The COLUMBUS trial,
(NCT01909453), is a two-part, international, randomized, open label
Phase 3 study evaluating the efficacy and safety of the combination
of binimetinib plus encorafenib to vemurafenib and encorafenib
monotherapy in 921 patients with locally advanced, unresectable or
metastatic melanoma with BRAF V600 mutation. Prior
immunotherapy treatment was allowed. Over 200 sites across
North America, Europe, South
America, Africa,
Asia and Australia participated in the study. Patients
were randomized into two parts:
- In Part 1, 577 patients were randomized 1:1:1 to receive 45mg
binimetinib plus 450mg encorafenib (COMBO450), 300mg encorafenib
alone, or 960mg vemurafenib alone. The dose of encorafenib in the
combination arm is 50% higher than the single agent maximum
tolerated dose of 300mg. A higher dose of encorafenib was
possible due to improved tolerability when combined with
binimetinib. The primary endpoint for the COLUMBUS trial was
a PFS comparison of COMBO450 versus vemurafenib. PFS is determined
based on tumor assessment (RECIST version 1.1 criteria) by a
Blinded Independent Central Review (BICR). Secondary endpoints
include a comparison of the PFS of encorafenib monotherapy to that
of COMBO450 and a comparison of overall survival (OS) for COMBO450
to that of vemurafenib alone.
In November 2016, results from
Part 1 were presented at the Society for Melanoma Research Annual
Congress. The study met its primary endpoint, with COMBO450
significantly improving PFS compared with vemurafenib alone. In the
analysis of the primary endpoint, the mPFS for patients treated
with COMBO450 was 14.9 months versus 7.3 months for patients
treated with vemurafenib; hazard ratio (HR) 0.54, (95% CI
0.41-0.71, P<0.001). As part of the trial design, the primary
analysis was based on a BICR of patient scans, while results by
local review at the investigative site were also analyzed. The
chart below outlines the mPFS results, as determined by both
assessments, for COMBO450 versus vemurafenib, COMBO450 versus
encorafenib, and encorafenib versus vemurafenib:
|
|
mPFS
BICR
|
|
mPFS Local
Review
|
COMBO450
vs.
Vemurafenib
|
|
COMBO450
|
Vemurafenib
|
|
COMBO450
|
Vemurafenib
|
|
14.9
months
|
7.3 months
|
|
14.8
months
|
7.3 months
|
|
HR (95% CI): 0.54
(0.41-0.71); P<0.001
|
|
HR (95% CI): 0.49
(0.37-0.64); P<0.001
|
|
COMBO450
vs.
Encorafenib
|
|
COMBO450
|
Encorafenib
|
|
COMBO450
|
Encorafenib
|
|
14.9
months
|
9.6 months
|
|
14.8
months
|
9.2 months
|
|
HR (95% CI): 0.75
(0.56-1.00); P=0.051
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.006
|
|
Encorafenib
vs.
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
Encorafenib
|
Vemurafenib
|
|
9.6 months
|
7.3 months
|
|
9.2 months
|
7.3 months
|
|
HR (95% CI): 0.68
(0.52-0.90); P=0.007
|
|
HR (95% CI): 0.70
(0.54-0.91); P=0.008
|
COMBO450 was generally well-tolerated and reported adverse
events (AEs) were overall consistent with previous bini/enco
combination clinical trial results in BRAF-mutant melanoma
patients. Grade 3/4 AEs which occurred in more than 5 percent of
patients receiving COMBO450 included increased
gamma-glutamyltransferase (GGT), increased blood creatine
phosphokinase (CK), and hypertension. The incidence of AEs of
special interest (toxicities commonly associated with commercially
available MEK+BRAF-inhibitor treatments), for patients receiving
COMBO450 included: rash (23 percent), pyrexia (18 percent), retinal
pigment epithelial detachment (13 percent) and photosensitivity (5
percent).
- In Part 2, 344 patients were randomized 3:1 to receive 45mg
binimetinib plus 300mg encorafenib or 300mg encorafenib alone. Part
2 is designed to provide additional data to help evaluate the
contribution of binimetinib to the combination of binimetinib and
encorafenib. As the comparison of COMBO450 to encorafenib in Part 1
did not achieve statistical significance, the statistical analysis
conducted in Part 2 is descriptive.
About BRAF-Mutant Melanoma
Melanoma is the
fifth most common cancer among men and the sixth most common cancer
among women in the United States,
with more than 87,000 new cases and over 9,700 deaths from the
disease expected in 2017. Up to 50 percent of patients with
metastatic melanoma have activating BRAF mutations, the most common
gene mutation in this patient population. Current marketed MEK/BRAF
combination agents have a run rate approaching $1 billion in annual worldwide sales.
About Binimetinib & Encorafenib
MEK and BRAF are
key protein kinases in the MAPK signaling pathway
(RAS-RAF-MEK-ERK). Research has shown this pathway regulates
several key cellular activities including proliferation,
differentiation, survival and angiogenesis. Inappropriate
activation of proteins in this pathway has been shown to occur in
many cancers, such as melanoma, colorectal and thyroid cancers.
Binimetinib is a late-stage small molecule MEK inhibitor and
encorafenib is a late-stage small molecule BRAF inhibitor, both of
which target key enzymes in this pathway. Binimetinib and
encorafenib are being studied in clinical trials in advanced cancer
patients, including the Phase 3 BEACON CRC trial with encorafenib
in combination with cetuximab with or without binimetinib in
patients with BRAF V600E-mutant colorectal cancer.
Binimetinib and encorafenib are investigational medicines and
are not currently approved in any country. Array BioPharma retains
exclusive rights to binimetinib and encorafenib in key markets
including the U.S., Japan,
Canada, Korea and Israel. Pierre Fabre will have exclusive
rights to commercialize both products in all other countries,
including Europe, Asia and Latin
America.
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. Seven registration studies are
currently advancing related to seven drugs: binimetinib (MEK162),
encorafenib (LGX818), selumetinib (partnered with AstraZeneca),
danoprevir (partnered with Roche), larotrectinib (partnered with
Loxo Oncology), tucatinib (partnered with Cascadian Therapeutics)
and ipatasertib (partnered with Genentech).
Array BioPharma 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 future development plans of binimetinib and
encorafenib, and the timing of the announcement of further results
of clinical trials for binimetinib and encorafenib; expectations
regarding the timing of regulatory filings for binimetinib and
encorafenib and regarding approval of binimetinib and encorafenib
for BRAF-mutant melanoma; expectations that events will
occur that will result in greater value for Array; and the
potential for the results of current and further clinical trials to
support regulatory approval or the marketing success of binimetinib
and encorafenib. 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, the determination by the FDA that results from
clinical trials are not sufficient to support registration or
marketing approval of binimetinib and encorafenib; 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 May 9, 2017.
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.
CONTACTS:
|
Tricia
Haugeto
|
|
(303)
386-1193
|
|
thaugeto@arraybiopharma.com
|
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