BOULDER, Colo., June 4, 2018 /PRNewswire/ -- Array
BioPharma Inc. (NASDAQ: ARRY) today announced updated results
from the Phase 3 COLUMBUS trial in BRAF-mutant advanced
melanoma. The results showed median overall survival (mOS) was 33.6
months for patients treated with the combination of encorafenib and
binimetinib compared to 16.9 months for patients treated with
vemurafenib as a monotherapy. The combination reduced the risk of
death compared to treatment with vemurafenib alone [hazard ratio
(HR) of 0.61, [95% CI 0.47, 0.79, p <0.0001]. The observed
efficacy of vemurafenib in the control arm is also consistent with
historical data, providing an additional benchmark for validating
the patient population and results observed in COLUMBUS. [1, 2] Further, the two-year
OS with combination therapy was 58%. These results will be part of
an oral presentation today at the American Society of Clinical
Oncology (ASCO) annual meeting in Chicago, Illinois and have been selected for
the "Best of ASCO" program.
Importantly, the presentation will include data showing limited
use of post-trial immunotherapy, which is consistent with other
published pivotal trials of BRAF and MEK-inhibitors in
BRAF-mutant advanced melanoma. [1, 3]
"The data presented today at ASCO demonstrate that the use of
subsequent immunotherapies was consistent across treatment groups,
indicating that these subsequent treatments are unlikely to have
contributed to the observed differences in survival," 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. "This further suggests
encorafenib and binimetinib could be a promising new treatment
option for patients with BRAF-mutant advanced melanoma."
Additionally, the updated median progression-free survival
(mPFS) results for patients treated with the combination of
encorafenib and binimetinib remained consistent with what was
previously reported at 14.9 months versus 7.3 months for patients
treated with vemurafenib [HR= 0.51, 95% CI 0.39–0.67;
p<0.0001].
As previously reported, the combination of encorafenib and
binimetinib was generally well-tolerated. Grade 3/4 adverse events
(AEs) that occurred in more than 5% of patients receiving the
combination were increased gamma-glutamyltransferase (GGT) (9%),
increased blood creatine phosphokinase (CK) (7%) and hypertension
(6%). The incidence of selected any grade AEs of special interest,
defined based on toxicities commonly associated with commercially
available BRAF+MEK-inhibitor treatments for patients receiving the
combination of encorafenib and binimetinib included: rash (22%),
serous retinopathy including retinal pigment epithelial detachment
(20%), pyrexia (18%) and photosensitivity (5%). Full safety results
of COLUMBUS Part 1 were published
in The Lancet Oncology.
A PDF of the ASCO COLUMBUS
presentation will be available on Array's website.
In the COLUMBUS trial, eligible
patients were randomized 1:1:1 to receive the combination of
encorafenib, 450 mg daily, plus binimetinib, 45 mg twice daily,
encorafenib 300 mg daily as a monotherapy, or vemurafenib 960 mg
twice daily as a monotherapy.
Data from Array's partnered programs with AstraZeneca, Genentech
and Loxo Oncology were also presented on the Array-invented
molecules selumetinib, ipatasertib and LOXO-292, respectively.
Array will host an encore webcast presentation of the
COLUMBUS trial data.
Encore
Webcast:
|
Presenter:
|
Keith T. Flaherty,
M.D.
|
Date:
|
Monday, June 4,
2018
|
Time:
|
11:15 a.m. Central
Time (12:15 p.m. Eastern Time)
|
Toll-Free:
|
(844)
464-3927
|
Toll:
|
(765)
507-2598
|
Pass
Code:
|
9615719
|
Webcast, including replay and conference call slides:
https://edge.media-server.com/m6/p/8juh6tcn
About Melanoma
Metastatic melanoma is the most serious and life-threatening type
of skin cancer and is associated with low survival rates. [4, 5]
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. [4, 6, 7, 8]
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 the
combination of encorafenib 450 mg daily and binimetinib 45 mg twice
daily (COMBO450), encorafenib, 300 mg daily alone (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 published in The
Lancet Oncology May 2018, 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 daily 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 COLUMBUS trial and the Phase 3 BEACON CRC 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] Ascierto PA, et al. Lancet Oncol.
2016;17:1248-1260.
[2] Robert C, et al. Eur J Cancer. 2015;51:S663-S664.
[3] Long GV, et al. Ann Oncol. 2017;28:1631-1639.
[4] Melanoma Skin Cancer. American Cancer Society. Available
at: https://www.cancer.org/cancer/melanoma-skin-cancer.html.
Accessed January 2018.
[5] A Snapshot of Melanoma. National Cancer Institute.
Available
at: https://seer.cancer.gov/statfacts/html/melan.html.
Accessed January 2018.
[6] Globocan 2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in
2012. http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.
Accessed January 2018.
[7] Klein O, et al. Eur J Cancer, 2013.
[8] American Cancer Society. What Causes Melanoma Skin Cancer?
2016.
https://www.cancer.org/cancer/melanoma-skin-cancer/causes-risks-prevention/what-causes.html.
Accessed April 11,
2018.
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 June 4, 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
Y&R PR
Erika Hackmann, Media Relations
(917) 538-3375
erika.hackmann@yr.com
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