BOULDER, Colo., March 22, 2018 /PRNewswire/ -- Array
BioPharma Inc. (Nasdaq: ARRY) today announced that detailed results
of its pivotal Phase 3 COLUMBUS trial for the treatment of patients
with BRAF-mutant advanced, unresectable or metastatic
melanoma were published in The Lancet Oncology. In the
analysis of the primary endpoint, the median progression-free
survival (mPFS) for patients treated with the combination of
encorafenib, 450 mg daily, plus binimetinib, 45 mg twice daily
(COMBO450) was 14.9 months versus 7.3 months for patients treated
with vemurafenib, 960 mg twice daily [hazard ratio (HR) 0.54, 95%
CI 0.41–0.71; p<0.0001].
The manuscript entitled "Encorafenib plus binimetinib versus
vemurafenib or encorafenib in patients with BRAF-mutant
melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3
trial," was published online on March 21,
2018. Array previously announced top line results from this
study in September 2016.
"A median progression-free survival of nearly 15 months with the
combination of encorafenib and binimetinib is clinically meaningful
for patients with advanced BRAF-mutant metastatic melanoma,"
said Keith T. Flaherty, M.D.,
Director of the Termeer Center for Targeted Therapy, Massachusetts
General Hospital Cancer Center and Professor of Medicine,
Harvard Medical School. "Further, a
median overall survival of 33.6 months, compared to 16.9 months
with vemurafenib monotherapy (HR of 0.61, 95% CI 0.47-0.79,
p<0.001), a secondary endpoint not included in this publication,
was recently announced. This further supplements the published data
and shows that the combination of encorafenib and binimetinib may
become a promising new therapy for patients with advanced
BRAF-mutant metastatic melanoma."
As previously reported, the combination of encorafenib and
binimetinib was generally well-tolerated. The median duration of
treatment was 51.2 weeks (27.1-79.7) for encorafenib and 50.6 weeks
(26.1-79.7) for binimetinib. The median dose intensity was 100%
(93-100) of planned doses of encorafenib and 99.6% (80-100) of
planned doses of binimetinib. The most common Grade 3/4 adverse
events (AEs) seen in more than 5% of patients were increased
gamma-glutamyltransferase (GGT) 9% (18/192 patients), increased
creatine phosphokinase 7% (13), and hypertension 6% (11) in the
encorafenib plus binimetinib group.
The U.S. Food and Drug Administration (FDA) is currently
reviewing the New Drug Applications to support use of the
combination of encorafenib and binimetinib for the treatment of
patients with BRAF-mutant advanced, unresectable or
metastatic melanoma. The FDA set a target action date under the
Prescription Drug User Fee Act (PDUFA) of June 30, 2018 for both applications. In addition,
the European Medicines Agency (EMA), as well as the Swiss Medicines
Agency (Swissmedic) and the Australian Therapeutic Goods
Administration (TGA), are reviewing the Marketing Authorization
Applications for encorafenib and binimetinib.
An update from the COLUMBUS trial will be presented at an
upcoming medical congress.
About Melanoma
Metastatic melanoma is the most serious and life-threatening type
of skin cancer and is associated with low survival rates. [1, 2]
There are about 200,000 new cases of melanoma diagnosed worldwide
each year, approximately half of which have BRAF mutations,
a key target in the treatment of metastatic melanoma. [1, 3, 4]
About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international,
randomized, open label Phase 3 trial evaluating the efficacy and
safety of the combination of encorafenib and binimetinib compared
to vemurafenib and encorafenib monotherapy in 921 patients with
locally advanced, unresectable or metastatic melanoma with
BRAFV600 mutation. Prior immunotherapy treatment
was allowed. Over 200 sites across North
America, Europe,
South America, Africa, Asia
and Australia participated in the
trial. Patients were randomized into two parts:
- In Part 1, 577 patients were randomized 1:1:1 to receive
COMBO450, encorafenib, 300 mg daily (ENCO 300), or vemurafenib, 960
mg twice daily alone. The dose of encorafenib in the combination
arm is 50% higher than the single agent maximum tolerated dose of
300 mg. A higher dose of encorafenib was possible due to improved
tolerability when combined with binimetinib. The primary endpoint
for the COLUMBUS trial was an mPFS comparison of the COMBO450 arm
versus vemurafenib. mPFS 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 mPFS
of COMBO450 arm to that of ENCO300 and a comparison of overall
survival (OS) in patients treated in the COMBO450 arm to that of
vemurafenib alone. Results from Part 1 of the COLUMBUS trial
previously presented at the 2016 Society for Melanoma Research
Annual Congress, showed that COMBO450 more than doubled mPFS in
patients with advanced BRAF-mutant melanoma, with a mPFS of
14.9 months compared with 7.3 months observed with vemurafenib [HR
0.54, (95% CI 0.41-0.71, p<0.0001)]. In the secondary mPFS
comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of
9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].
- In Part 2, 344 patients were randomized 3:1 to receive
encorafenib 300 mg plus binimetinib 45 mg twice daily (COMBO300) or
ENCO300. Part 2 was designed to provide additional data to help
evaluate the contribution of binimetinib to the combination of
encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the
COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical
significance, the protocol specified analysis of OS is
descriptive.
About Encorafenib and Binimetinib
BRAF and MEK 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 including melanoma and colorectal cancer. Encorafenib
is a late-stage small molecule BRAF inhibitor and binimetinib is a
late-stage small molecule MEK inhibitor, both of which target key
enzymes in this pathway. Encorafenib and binimetinib are being
studied in clinical trials in advanced cancer patients, including
the Phase 3 BEACON CRC trial and the Phase 3 COLUMBUS
trial.
Array BioPharma has exclusive rights to encorafenib and
binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical
exclusive rights to commercialize both products in Japan and South
Korea and Pierre Fabre
exclusive rights to commercialize both products in all other
countries, including Europe,
Asia and Latin America. Encorafenib and binimetinib are
investigational medicines and are not currently approved in any
country.
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 and other
conditions. Ten registration studies are currently advancing
related to eight Array-owned or partnered drugs: encorafenib
(LGX818), binimetinib (MEK162), ARRY-797, selumetinib (partnered
with AstraZeneca), danoprevir (partnered with Roche), ipatasertib
(partnered with Genentech), larotrectinib (partnered with Loxo
Oncology) and tucatinib (partnered with Seattle Genetics). For more
information on Array, please go to www.arraybiopharma.com.
References
[1] Melanoma Skin Cancer. American Cancer Society. Available
at: https://www.cancer.org/cancer/melanoma-skin-cancer.html.
Accessed January 2018.
[2] A Snapshot of Melanoma. National Cancer Institute.
Available
at: https://seer.cancer.gov/statfacts/html/melan.html.
Accessed January 2018.
[3] Globocan 2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in
2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessed January 2018.
[4] Klein O, et al. Eur J Cancer, 2013.
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
encorafenib and binimetinib; expectations regarding approval of
encorafenib and binimetinib for BRAF-mutant melanoma and
timing of such approvals; expectations that events will occur that
will result in greater value for Array; and the potential for the
results of current and future clinical trials to support regulatory
approval or the marketing success of encorafenib and binimetinib.
Specifically, there is no assurance that results from the BEACON
CRC and COLUMBUS trials will satisfy the requirements of regulatory
authorities necessary for approval. 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, EMA or other regulatory agencies that
results from clinical trials are not sufficient to support
registration or marketing approval of encorafenib and binimetinib;
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 and to manufacture drug substance and product within and
outside the U.S.; our ability to grow and successfully develop
commercialization capabilities; 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 March 22, 2018. 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:
Investor Relations
Array BioPharma
Andrea N.
Flynn, Ph.D.
Senior Director, Investor Relations & Corporate
Communications
(303) 381-6600
ir@arraybiopharma.com
Media
Russo Partners, LLC
David Schull or Travis Kruse, Ph.D.
(212) 845-4271
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