EMD Serono Initiates Phase II Study of Anti-PD-L1 Antibody MSB0010718C in Metastatic Merkel Cell Carcinoma

July 29, 2014

ROCKLAND, Massachusetts, July 29, 2014 /PRNewswire/ –

        - First patient begins treatment in an international Phase II study
          investigating the efficacy and safety of MSB0010718C in patients with metastatic
          Merkel cell carcinoma (mMCC)
        - mMCC is a rare and aggressive skin cancer lacking effective treatments
        - MSB0010718C is also currently being explored in a seven cohort Phase I
          clinical trial for the treatment of solid tumors that aims to recruit 590 patients

EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, today announced the
initiation of an international Phase II study designed to assess the efficacy and safety
of MSB0010718C, an investigational fully human IgG1 monoclonal antibody that binds to
programmed death-ligand 1 (PD-L1). This multicenter, single-arm, open-label study is being
conducted in patients with metastatic Merkel cell carcinoma (mMCC), a rare and aggressive
type of skin tumor,[1],[2] who have previously received one line of chemotherapy. It is
expected to recruit 84 patients across Asia Pacific, Australia, Europe and North America.
The primary endpoint of the study is overall response.

The PD-L1/PD-1 pathway is implicated as a major mechanism by which tumors evade
elimination by the immune system.[3] The PD-L1 molecule is expressed in many cancer types,
including mMCC.[3],[4] MSB0010718C, which blocks the interaction of PD-L1 with its
receptor PD-1, may have the potential to restore effective anti-tumor T-cell responses and
thereby to inhibit tumor growth.

Immune mechanisms are implicated in the pathogenesis of MCC, with an increased risk
observed in immunosuppressed individuals.[5] MCC also is associated with the presence of
the Merkel cell polyomavirus, which may have a role in tumor formation.[6] Globally, the
incidence of MCC is increasing, and outcomes for patients with this disease are
poor.[1],[2] Therefore, new treatment approaches are required to improve the outcome of
patients with this type of cancer.

“We believe that modulating the immune system by targeting PD-L1 represents a
promising new approach in the treatment of this aggressive cancer, especially considering
that many of the predisposing factors for mMCC seem to be related to functional
disruptions of the immune system,” said Helen Sabzevari, Senior Vice President of
Immuno-Oncology at the biopharmaceutical division of Merck KGaA, Darmstadt, Germany. “Our
anti-PD-L1 compound may present a potential new approach for the treatment of mMCC
patients. The initiation of this Phase II study is an important milestone, as we endeavor
to help those suffering from mMCC, a devastating disease with significant unmet need.”

In addition to this new study in mMCC, MSB0010718C is currently being explored in a
Phase I clinical trial for the treatment of solid tumors. The study aims to recruit 590
patients and has enrolled 422 patients to date. On June 1, 2014, EMD Serono presented
initial data from this dose escalation study in solid tumors at the annual American
Society of Clinical Oncology (ASCO) meeting in Chicago.[7] This study is currently
recruiting patients into expansion cohorts in seven cancer types: castrate-resistant
prostate cancer, colorectal cancer, gastric/gastroesophogeal cancer, melanoma, metastatic
breast cancer, non-small cell lung cancer and ovarian cancer.

For more information on the study, please visit http://www.clinicaltrials.gov, or
click here [https://clinicaltrials.gov/ct2/show/NCT02155647?term=NCT02155647&rank=1 ].


        1) Hughes MP, et al. Curr Dermatol Rep 2014;3:46-53.
        2) Kaae J, et al. J Natl Cancer Inst 2010;102(11):793-801.
        3) Lipson EJ, et al. Cancer Immunol Res 2013;1(1):54-63.
        4) McDermott DF and Atkins MB. Cancer Med 2013; 2(5):662-73.
        5) Bhatia S, et al. Curr Oncol Rep 2011;13(6):488-97.
        6) Feng H, et al. Science 2008;319(5866):1096-100.
        7) Heery CR, et al. J Clin Oncol 2014;32:5(Suppl.) Abstract No. 3064.

About MSB0010718C

MSB0010718C is an investigational fully human IgG1 monoclonal antibody that binds to
the PD-L1 (programmed death-ligand 1) protein, which is present at high levels in many
cancer types. By competitively blocking the interaction with PD-1 receptors, it is
believed that MSB0010718C thereby restores anti-tumor T-cell responses.

About Merkel cell carcinoma (MCC)

MCC is a rare and aggressive disease in which cancer cells form in the top layer of
the skin, close to nerve endings. MCC, which is also known as neuroendocrine carcinoma of
the skin or trabecular cancer, often starts in those areas of skin that are most often
exposed to the sun, including the head and neck, arms, legs, and trunk. Risk factors for
MCC include sun exposure and having a weak immune system (i.e., solid-organ transplant
recipients, people with HIV/AIDS and people with other cancers, such as chronic
lymphocytic leukemia, are at higher risk). Caucasian males over age 50 are at increased

MCC tends to metastasize at an early stage, spreading initially to nearby lymph nodes,
and then potentially to more distant areas in the body, including other lymph nodes or
areas of skin, lungs, brain, bones, or other organs.

Current treatment options for MCC include surgery, radiation and chemotherapy.
Treatment for metastatic or Stage IV MCC is generally palliative.

About EMD Serono, Inc.

EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany, is a specialized
biopharmaceutical company dedicated to developing therapies with groundbreaking potential.
The company has strong market positions in neurology, endocrinology and in reproductive
health. In addition, EMD Serono has an enduring commitment to solve the unsolvable, with
state-of-the-art science dedicated to developing new therapies in our core focus areas of
neurology, oncology, immuno-oncology and immunology. With a long-standing history of
industry expertise and a dedication to shape the future of healthcare, the company’s US
footprint continues to grow, with approximately 1,000 employees around the country and
fully integrated commercial, clinical and research operations in the company’s home state
of Massachusetts.

For more information, please visit http://www.emdserono.com.

About Merck KGaA, Darmstadt, Germany

Merck KGaA of Darmstadt, Germany, is a leading company for innovative and top-quality
high-tech products in the pharmaceutical and chemical sectors. Its subsidiaries in Canada
and the United States operate under the umbrella brand EMD. Around 38,000 employees work
in 66 countries to improve the quality of life for patients, to further the success of
customers and to help meet global challenges. The company generated total revenues of
EUR11.1 billion in 2013 with its four divisions: Biopharmaceuticals, Consumer Health,
Performance Materials and Life Science Tools. Merck KGaA of Darmstadt, Germany is the
world’s oldest pharmaceutical and chemical company – since 1668, the name has stood for
innovation, business success and responsible entrepreneurship. Holding an approximately 70
percent interest, the founding family remains the majority owner of the company to this


Source: PR Newswire

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