Merck Partners with Array BioPharma and Pierre Fabre to Initiate BRAF-mutant CRC Phase III Trial

Darmstadt, Germany (ots/PRNewswire) -

Not intended for UK- or US-based media

- BEACON CRC trial will assess efficacy of combination regime
Erbitux® (cetuximab), binimetinib and encorafenib in BRAF-mutant
metastatic colorectal cancer (mCRC)

Merck, a leading science and technology company, jointly announced
with Array BioPharma Inc. and Pierre Fabre, the initiation of a
prospective, randomized, global Phase III clinical trial of
BRAF-mutant metastatic colorectal cancer (mCRC), investigating a new
combination of Erbitux® (cetuximab), a standard-of-care treatment for
RAS wild-type mCRC, plus encorafenib with or without binimetinib. The
BEACON CRC (Binimetinib, Encorafenib And Cetuximab Combined to treat
BRAF-mutant Colorectal Cancer) trial will assess the efficacy and
safety of these two novel combinations in patients with BRAF-mutant
tumors, compared with investigator's choice of Erbitux plus
irinotecan or Erbitux plus FOLFIRI.

(Logo: http://photos.prnewswire.com/prnh/20151207/293543LOGO )

(Logo: http://photos.prnewswire.com/prnh/20151019/278051LOGO )

"This trial looking specifically at BRAF-mutated tumors
exemplifies our ongoing commitment to exploring Erbitux as an
'anchor' treatment in combination with other therapies," said Luciano
Rossetti, Executive Vice President, Head of Global Research &
Development at the biopharma business of Merck. "There is a clear
need for effective treatment regimens for the BRAF-mutant mCRC
population; the results of the BEACON CRC trial will hopefully
provide us with the prospective information we need to take us one
step closer to achieving that goal."

Colorectal cancer (CRC) is one of the most challenging types of
cancers, with an estimated 10 percent of CRCs associated with an
oncogenic mutation in the BRAF gene.[1] Studies have observed that
patients with BRAF-mutant mCRC have shorter progression-free survival
and overall survival.[2] Additional treatment regimens are needed
that can effectively combat these cancers.

"Historical studies suggest that BRAF-mutant colorectal cancer
patients who have progressed after first-line systemic treatment have
an estimated median overall survival of less than 6 months," said Dr.
Josep Tabernero, MD, PhD, Head of Medical Oncology and the Institute
of Oncology at Vall d'Hebron University Hospital. "The BEACON CRC
trial will explore innovative combinations which have the potential
to offer new treatment options to these patients, who currently have
few good choices remaining."

"We are pleased to join Merck on this innovative trial for
patients with BRAF-mutant metastatic colorectal cancer," said Victor
Sandor, MD, Chief Medical Officer of Array BioPharma. "The
encouraging results from our Phase II study suggest that concurrent
inhibition of EGFR and enzymes in the MAPK signaling pathway has the
potential to improve outcomes for this patient population, and we
look forward to the results of this further investigation."

Approximately 650 patients are expected to be enrolled by 2018
and, after a lead-in period to assess the safety and tolerability of
Erbitux plus encorafenib (BRAF inhibitor) and binimetinib (MEK
inhibitor), will be randomized to receive one of the two novel
combinations, or investigator's choice. The primary endpoint of the
trial is overall survival. Key secondary endpoints include
progression-free survival, objective response rate, duration of
response, safety and tolerability. The trial will also assess
health-related quality of life.

References

1. Barras D. Biomark Cancer. 2015;7(Suppl 1):9-12.
2. Saridaki Z. PLoS One. 2013 Dec 18;8(12):e84604. doi: 10.1371.
3. Vaughn CP et al. Genes Chromosomes Cancer 2011;50(5):307?12.
4. Bokemeyer C et al. J Clin Oncol 2014;32:(Suppl 4): abstr 3505.
5. Van Cutsem E et al. J Clin Oncol 2015;33(7):692-700.
6. Stintzing S et al. Ann Oncol 2014;25(Suppl 4) abstr LBA11.
7. Lenz H et al. Ann Oncol 2014;25(Suppl 4) abstr 501O.
8. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C,
Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer
Incidence and Mortality Worldwide: IARC CancerBase No. 11
[Internet]. Lyon, France: International Agency for Research on
Cancer; 2013. Available from: http://globocan.iarc.fr , accessed
June 2015.

About BRAF Mutations

BRAF is an important actor in the epidermal growth factor
receptor(EGFR)-mediated mitogen-activated protein kinase (MAPK)
pathway, which strongly impacts cell growth and proliferation, as
well as cell migration, cell death and cell survival.[1]

About mCRC

Approximately half of patients with mCRC have RAS wild-type tumors
and half have RAS mutant tumors.[3] Results from studies assessing
RAS mutation status in patients with mCRC have shown that
anti-epidermal growth factor receptor (EGFR) monoclonal antibody
therapies, such as Erbitux® (cetuximab), can improve outcomes in
patients with RAS wild-type mCRC.[4]-[7] CRC is the third most common
cancer worldwide, with an estimated incidence of more than 1.36
million new cases annually.[7] An estimated 694,000 deaths from CRC
occur worldwide every year, accounting for 8.5% of all cancer deaths
and making it the fourth most common cause of death from cancer.[8]
Almost 55% of CRC cases are diagnosed in developed regions of the
world, and incidence and mortality rates are substantially higher in
men than in women.[8]

About Erbitux (cetuximab)

Erbitux® is a highly active IgG1 monoclonal antibody targeting the
epidermal growth factor receptor (EGFR). As a monoclonal antibody,
the mode of action of Erbitux is distinct from standard non-selective
chemotherapy treatments in that it specifically targets and binds to
the EGFR. This binding inhibits the activation of the receptor and
the subsequent signal-transduction pathway, which results in reducing
both the invasion of normal tissues by tumor cells and the spread of
tumors to new sites. It is also believed to inhibit the ability of
tumor cells to repair the damage caused by chemotherapy and
radiotherapy and to inhibit the formation of new blood vessels inside
tumors, which appears to lead to an overall suppression of tumor
growth.

The most commonly reported side effect with Erbitux is an
acne-like skin rash that seems to be correlated with a good response
to therapy. In approximately 5% of patients, hypersensitivity
reactions may occur during treatment with Erbitux; about half of
these reactions are severe.

Erbitux has already obtained market authorization in over 90
countries world-wide for the treatment of colorectal cancer and for
the treatment of squamous cell carcinoma of the head and neck
(SCCHN). Merck licensed the right to market Erbitux outside the US
and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly
and Company, in 1998. Merck has an ongoing commitment to the
advancement of oncology treatment and is currently investigating
novel therapies in highly targeted areas.

About Binimetinib & Encorafenib

MEK and RAF are key protein kinases in the
RAS-RAF-MEK-ERK-pathway. Research has shown this pathway regulates
several key cellular activities including proliferation,
differentiation, migration, survival and angiogenesis. Inappropriate
activation of proteins in this pathway has been shown to occur in
many cancers, such as non-small cell lung cancer, melanoma,
colorectal and thyroid cancer. Binimetinib is a small molecule MEK
inhibitor and encorafenib is a small molecule RAF inhibitor, each of
which target key enzymes in this pathway. There are three active
Phase III trials which include these products: NRAS-mutant melanoma
(NEMO, with binimetinib), BRAF-mutant melanoma (COLUMBUS, with
binimetinib and encorafenib) and BRAF-mutant colorectal cancer
(BEACON CRC, with binimetinib and encorafenib).

All Merck Press Releases are distributed by e-mail at the same
time they become available on the Merck Website. Please go to
http://www.merckgroup.com/subscribe to register online, change your
selection or discontinue this service.

For further details and press materials about Merck products
please visit www.merckgroup.com/media-center-oncology .

About Merck

Merck is a leading science and technology company in healthcare,
life science and performance materials. Around 50,000 employees work
to further develop technologies that improve and enhance life - from
biopharmaceutical therapies to treat cancer or multiple sclerosis,
cutting-edge systems for scientific research and production, to
liquid crystals for smartphones and LCD televisions. In 2015, Merck
generated sales of EUR 12.85 billion in 66 countries.

Founded in 1668, Merck is the world's oldest pharmaceutical and
chemical company. The founding family remains the majority owner of
the publicly listed corporate group. Merck, Darmstadt, Germany holds
the global rights to the Merck name and brand. The only exceptions
are the United States and Canada, where the company operates as EMD
Serono, MilliporeSigma and EMD Performance Materials.

Contact: Gangolf Schrimpf +49-6151-72-9591

Frankfurter Strasse 250

64293 Darmstadt, Germany

Hotline
+49-6151-72-5000

merckgroup.com

Head Media Relations -62445

Spokesperson: -9591 / -7144 / -6328

Fax
+49 6151 72 3138

media.relations@merckgroup.com

ots Originaltext: Merck KGaA
Im Internet recherchierbar: http://www.presseportal.de