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

PR57467

DARMSTADT, Germany, Jul 29, 2014 /PRN=KYODO JBN/ --

- 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

Merck Serono, the biopharmaceutical division of Merck, 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 Merck Serono. "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,

Merck 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/gastroesophageal cancer, melanoma, metastatic breast cancer, non-small

cell lung cancer and ovarian cancer.

References

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

risk.

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 Merck Serono

Merck Serono is the biopharmaceutical division of Merck. With headquarters in

Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help

patients with cancer, multiple sclerosis, infertility, endocrine and metabolic

disorders as well as cardiovascular diseases. In the United States and Canada,

EMD Serono operates as a separately incorporated subsidiary of Merck Serono.

Merck Serono discovers, develops, manufactures and markets prescription

medicines of both chemical and biological origin in specialist indications. We

have an enduring commitment to deliver novel therapies in our core focus areas

of neurology, oncology, immuno-oncology and immunology.

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

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SOURCE: Merck Serono