BOULDER, Colo., June 23, 2018 /PRNewswire/ -- Array
BioPharma Inc. (NASDAQ: ARRY) today announced updated safety and
efficacy results, including OS, from the safety lead-in of the
Phase 3 BEACON CRC trial evaluating the triplet combination of
encorafenib, a BRAF inhibitor, binimetinib, a MEK inhibitor and
cetuximab, an anti-EGFR antibody, in patients with
BRAFV600E-mutant metastatic colorectal cancer
(CRC). The results showed that, at the time of analysis, the OS
data were fully mature through 12.6 months and that the median OS
had not yet been reached. The one-year overall survival rate for
this cohort was 62%. These data were presented in an oral
presentation on Saturday, June 23, at
the ESMO 20th World Congress on Gastrointestinal Cancer
in Barcelona, Spain.
The median progression-free survival (mPFS) for patients treated
with the triplet was 8 months [95% CI 5.6-9.3] and is similar
between patients receiving one prior line of therapy and patients
receiving two prior lines of therapy. The confirmed overall
response rate (ORR) was 48% and among the 17 patients who received
only one prior line of therapy the ORR was 62%.
"The results of the BEACON CRC safety lead-in demonstrate
substantial improvements in efficacy outcomes when compared to
current approved standard of care benchmarks in patients with
BRAF-mutant metastatic CRC. The median progression-free
survival of 8 months is a meaningful improvement compared to the
benchmark of about 2 months, and the overall survival of 62% at 12
months is very promising given that with current approved standards
of care, half of patients will succumb to their disease within 4 to
6 months," said Axel Grothey, M.D.,
Division of Hematology/Oncology, Mayo Clinic. "These data
underscore the potential of this triplet combination to benefit
patients with BRAFV600E-mutant metastatic CRC,
who, despite their poor prognosis, currently have limited effective
treatment options."
The triple combination was generally well-tolerated with no
unexpected toxicities. The most common grade 3 or 4 adverse events
seen in at least 10% of patients were fatigue (13%), anemia (10%),
increased blood creatine kinase (10%) and increased aspartate
aminotransferase (10%).
The presentation also referenced updated, mature Phase 2 results
for the doublet of encorafenib and cetuximab that showed a mOS of
9.3 months, mPFS of 4.2 months and an ORR of 24%. The data cutoff
for that analysis was January 2018
with the last patient enrolled in April of 2015; a detailed
presentation of these data will occur at a future medical
congress.
Enrollment in the randomized portion of the BEACON CRC trial is
ongoing. Patients interested in participating in this trial may
talk to their doctor to have their tumor tested for the BRAF
mutation for eligibility to enroll in this new and important trial.
Further details on the trial are available at clinicaltrials.gov
(NCT02928224).
A PDF of the ESMO World Congress on Gastrointestinal Cancer
presentation will be available on Array's website.
Array will host an encore webcast presentation of the BEACON CRC
safety lead-in data.
Encore Investor
Webcast:
|
Presenter:
|
Axel Grothey, M.D.,
Division of Hematology/Oncology, Mayo Clinic
|
Date:
|
Saturday, June
23
|
Time:
|
4:30 pm CET (10:30 am
ET)
|
Toll-Free:
|
(844)
464-3927
|
Toll:
|
(765)
507-2598
|
Pass
Code:
|
8588348
|
Webcast, including replay and conference call slides:
https://edge.media-server.com/m6/p/bn2j2g45
About Colorectal Cancer
Worldwide, colorectal cancer
is the third most common type of cancer in men and the second most
common in women, with approximately 1.4 million new diagnoses in
2012. Globally in 2012, approximately 694,000 deaths were
attributed to colorectal cancer. [1] In the U.S. alone, an
estimated 140,250 patients will be diagnosed with cancer of the
colon or rectum in 2018, and approximately 50,000 are estimated to
die of their disease. [2] In the U.S., BRAF mutations are
estimated to occur in 10% to 15% of patients with colorectal cancer
and represent a poor prognosis for these patients. [3-6] The risk
of mortality in CRC patients with the BRAFV600E
mutation is more than two times higher than for those with
wild-type BRAF. [7] Several approved standard of care
benchmarks for patients with BRAF-mutant CRC whose disease
has progressed after one or two prior lines of therapy, range
between 4% to 8% ORR, 1.8 and 2.5 months mPFS and 4 and 6 months
mOS. [8-14] Recently published results (April 2018; June
2017) from BRAF-containing triplet regimens in this
population resulted in an mOS of approximately 9 months.
Specifically, the triplet combination of dabrafenib, a BRAF
inhibitor, trametinib, a MEK inhibitor and panitumumab, a
monoclonal EGFR antibody, demonstrated an mOS of 9.1 months (n=91)
and the triplet combination of vemurafenib, a BRAF inhibitor,
cetuximab and irinotecan, a chemotherapy, demonstrated an mOS of
9.6 months (n=49). [8,15] Based on recent prospective historical
data, the prevalence of microsatellite instability-high (MSI-H) in
tumors from patients with metastatic BRAF-mutant CRC ranged
from 14% in a recent Phase 1b/2 trial
(NCT01719380) (Array, data on file) to 18% in a recent Southwestern
Oncology Group (SWOG) randomized phase 2 trial.
[8]
About BEACON CRC
BEACON CRC is a randomized,
open-label, global trial evaluating the efficacy and safety of
encorafenib, binimetinib and cetuximab in patients with
BRAF-mutant metastatic CRC whose disease has progressed
after one or two prior regimens. BEACON CRC is the first and only
Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in
BRAF-mutant advanced CRC. Thirty patients were treated in
the safety lead-in and received the triplet combination
(encorafenib 300 mg daily, binimetinib 45 mg twice daily and
cetuximab per label). Of the 30 patients, 29 had a
BRAFV600E mutation. MSI-H, resulting from
defective DNA mismatch repair, was detected in only 1 patient. As
previously announced, the triplet combination demonstrated good
tolerability, supporting initiation of the randomized portion of
the trial.
The randomized portion of the BEACON CRC trial is designed to
assess the efficacy of encorafenib in combination with cetuximab
with or without binimetinib compared to cetuximab and
irinotecan-based therapy. Approximately 615 patients are expected
to be randomized 1:1:1 to receive triplet combination, doublet
combination (encorafenib and cetuximab) or the control arm
(irinotecan-based therapy and cetuximab). The primary endpoint of
the trial is overall survival of the triplet combination compared
to the control arm. Secondary endpoints address efficacy of the
doublet combination compared to the control arm, and the triplet
combination compared to the doublet therapy. Other secondary
endpoints include PFS, ORR, duration of response, safety and
tolerability. Health related quality of life data will also be
assessed. The trial is being conducted at over 200 investigational
sites in North America,
South America, Europe and the Asia
Pacific region. Patient enrollment is expected to be
completed in 2018.
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.
The U.S. Food and Drug Administration (FDA) is currently
reviewing the New Drug Applications (NDAs) to support use of the
combination of encorafenib and binimetinib for the treatment of
patients with BRAFV600Eor
BRAFV600K-mutant, 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. 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 (MAAs) submitted by
Pierre Fabre and Japan's Pharmaceuticals and Medical Devices
Agency (PMDA) has accepted the Manufacturing and Marketing Approval
(MMA) applications submitted by Ono Pharmaceutical Co, Ltd.
Encorafenib and binimetinib are investigational medicines and
are not currently approved in any country.
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. The
BEACON CRC trial is being conducted with support from Pierre Fabre and Merck KGaA, Darmstadt,
Germany (support is for sites
outside of North 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. Nine registration studies are
currently advancing related to seven Array-owned or partnered
drugs: encorafenib (LGX818), binimetinib (MEK162), ARRY-797,
selumetinib (partnered with AstraZeneca), ipatasertib (partnered
with Genentech), larotrectinib (partnered with Loxo Oncology) and
tucatinib (partnered with Seattle Genetics). Ganovo®
(danoprevir, partnered with Roche) was recently approved in
China for the treatment of viral
hepatitis C. For more information on Array, please go to
www.arraybiopharma.com.
References
[1] Global Cancer Facts & Figures 3rd
Edition. American Cancer Society. Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-3rd-edition.pdf.
Accessed January 2018.
[2] Cancer Facts & Figures 2018. American Cancer Society.
Available at:
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-2018.pdf.
Accessed January 2018.
[3] Saridaki et al., PLoS One. 2013
[4] Loupakis et al.,
Br J Cancer. 2009
[5] Sorbye H, et al. PLoS One. 2015
[6] Vecchione, et al. Cell. 2016
[7] Safaee Ardekani G, Jafarnejad SM, Tan L, et al. The prognostic
value of BRAF mutation in colorectal cancer and melanoma: a
systematic review and meta-analysis. PLoS One.
2012;7(10):e47054.
[8] Kopetz et al., ASCO 2017
[9] De Roock et al.,
Lancet Oncol, 2010
[10] Ulivi et al., J Transl Med.
2012
[11] Peeters et al., ASCO 2014
[12]
Saridaki et al., PLoS One. 2013
[13] Loupakis et al.,
Br J Cancer. 2009
[14] Seymour et al., Lancet Oncol, 2013 (supplementary
appendix)
[15] Corcoran et al., Cancer Discovery, 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 23, 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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