BOULDER, Colo. and CASTRES,
France, Jan. 20, 2018 /PRNewswire/ -- Array
BioPharma Inc. (Nasdaq: ARRY) and Pierre
Fabre today announced updated results from the 30 patient
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 BRAF-mutant metastatic colorectal cancer (CRC) whose
disease has progressed after one or two prior regimens. The data
were presented at the ASCO 2018 Gastrointestinal Cancers Symposium
in San Francisco,
California.
In patients with the BRAFV600E mutation, the
estimated median progression-free survival (mPFS) at the time of
analysis was 8 months. The confirmed overall response rate
(ORR)* in patients with the BRAFV600E
mutation was 48%, and 3 patients achieved complete responses (CR).
Further, the ORR was 62% in the 16 patients (10/16) who received
only one prior line of therapy. These data represent substantial
improvements compared to several separate historical published
standard of care benchmarks for this population.
"We are very excited about these safety lead-in results, which
show both an unprecedented progression-free survival and overall
response rate in patients with BRAFV600-mutant
colorectal cancer," said Scott
Kopetz, M.D., Ph.D., FACP, Associate Professor, Department
of Gastrointestinal Medical Oncology, Division of Cancer Medicine,
The University of Texas MD Anderson
Cancer Center. "To put these data in context, the observed median
progression-free survival of 8 months exceeds historical benchmarks
of approximately 2 months for median progression-free survival, and
4 to 6 months for median overall survival, with current standards
of care in this patient population. These results demonstrate the
potential of the triplet combination to benefit this population of
patients who currently have very limited effective treatment
options."
In the safety lead-in, the triplet combination was generally
well-tolerated. Two patients discontinued treatment due to adverse
events (AEs) with only one of these considered related to
treatment. The most common grade 3 or 4 AEs seen in at least 10% of
patients were fatigue (4/30), urinary tract infection (3/30),
increased aspartate aminotransferase (AST; 3/30) and increased
blood creatine kinase (CK; 3/30).
All patients with elevated baseline levels of the tumor markers
CEA and CA19-9 had a reduction from baseline, with similar and
substantial (median 83% - 96%) reductions across both markers in
patients with objective responses and those with stable
disease.
The 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 ASCO 2018 Gastrointestinal Cancers Symposium
presentation can be found on Array's website:
http://www.arraybiopharma.com/download_file/282/
*Overall response rate (ORR) = Complete response (CR) + Partial
response (PR)
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. 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. Microsatellite
instability-high (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 will be conducted at over 250
investigational sites in North
America, South America,
Europe and the Asia Pacific region. Patient enrollment is
expected to be completed in 2018.
BEACON CRC is the first and only Phase 3 trial designed to test
a BRAF/MEK combo targeted therapy in BRAF-mutant advanced
CRC. Phase 2 trial results were presented at the 2016 ASCO annual
meeting. [1] In the doublet arm of encorafenib and cetuximab,
median overall survival (mOS) exceeded one year, which is more than
double several separate historical published standard of care
benchmarks for this population. [1-7] Further, the ORR was 22% and
the mPFS was 4.2 months. [1] Historical published ORR and mPFS
benchmarks in this patient population using standard of care
regimens range between 4% to 8% and 1.8 and 2.5 months,
respectively. [5-8]
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. Of these, nearly 750,000 were diagnosed in men, and 614,000
in women. Globally in 2012, approximately 694,000 deaths were
attributed to colorectal cancer. 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. [9] 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, 4, 10, 11] Based
on recent prospective historical data, the prevalence of 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.
[7]
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 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) is reviewing the Marketing
Authorization Applications for encorafenib and binimetinib.
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), selumetinib
(partnered with AstraZeneca), danoprevir (partnered with Roche),
ipatasertib (partnered with Genentech), larotrectinib (partnered
with Loxo Oncology) and tucatinib (partnered with Cascadian
Therapeutics).
About Pierre Fabre
With
a portfolio representing a continuum of activities spanning from
prescription drugs and consumer healthcare products to
dermo-cosmetics, Pierre Fabre is the
2nd largest dermo-cosmetics laboratory in the world, the 2nd
largest private French pharmaceutical group and the market leader
in France for products sold over
the counter in pharmacies. Its portfolio includes several global
brands and franchises among which Eau Thermale Avène - the
worldwide dermo-cosmetic market leader - Klorane, Ducray, René
Furterer, A-Derma, Galénic, Elancyl, Naturactive, Pierre Fabre
Health Care, Pierre Fabre Oral Care, Pierre Fabre Dermatologie and
Pierre Fabre Oncologie.
In 2016, Pierre Fabre generated
2,282 million euros in revenues, of
which 60% came from its international business and 59% from its
dermo-cosmetics division. Pierre
Fabre, which has always been headquartered in the South-West
of France, counts more than 13,000
employees worldwide, owns subsidiaries and offices in 47 countries
and enjoys distribution agreements in over 130 countries. In 2016,
Pierre Fabre dedicated ca.
195 million euros to its R&D
efforts, split between oncology, central nervous system, consumer
healthcare, dermatology and dermo-cosmetics.
Pierre Fabre is 86%-owned by the
Pierre Fabre Foundation, a government-recognized public-interest
foundation, and secondarily by its own employees through an
international employee stock ownership plan.
The independent French certification group AFNOR audited
Pierre Fabre for its corporate
social responsibility policy at the "exemplary" level, according to
the ISO 26000 standard for CSR.
To find out more about Pierre
Fabre, please go to www.pierre-fabre.com
References
[1] Tabernero et al., ASCO 2016
[2] Ulivi et al., J Transl Med. 2012
[3] Saridaki et al., PLoS One. 2013
[4] Loupakis et al.,
Br J Cancer. 2009
[5] De Roock et al., Lancet Oncol, 2010
[6] Peeters et al., ASCO 2014
[7] Kopetz et al., ASCO 2017
[8] Seymour et al., Lancet Oncol, 2013 (supplementary
appendix)
[9] 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.
[10] Sorbye H, et al. PLoS One. 2015
[11] Vecchione, et al. Cell. 2016
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; 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 trial will satisfy the
requirements of regulatory authorities necessary to file an
application for marketing approval, or that if such application is
accepted, that it will be approved. 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 January 20, 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
Pierre Fabre
Valérie
Roucoules
Deputy Director Pierre Fabre Médicament (Pharmaceutical)
Communications
(33) 1 49 10 83 84
valerie.roucoules@pierre-fabre.com
Media
Axicom
Chelsey
Berger
(718) 915-3125
Chelsey.Berger@axicom.com
View original content with
multimedia:http://www.prnewswire.com/news-releases/combination-of-encorafenib-binimetinib-and-cetuximab-demonstrated-an-8-month-median-progression-free-survival-in-braf-mutant-colorectal-cancer-in-updated-safety-lead-in-results-from-beacon-phase-3-trial-300585563.html
SOURCE Array BioPharma Inc.