Merck Serono: Phase III Trial of Cilengitide Did Not Meet Primary Endpoint in Patients With Newly Diagnosed Glioblastoma

Patients with newly diagnosed glioblastoma and methylated MGMT gene promoter status did not live significantly longer when treated with cilengitide plus chemoradiotherapy

Darmstadt, Germany, 1-3-2013 — /europawire.eu/ — Merck Serono, a division of Merck, Darmstadt, Germany, announced today that the Phase III CENTRIC^a
trial of the investigational integrin inhibitor cilengitide did not meet its primary endpoint of significantly increasing overall survival when added to the current standard chemoradiotherapy regimen (temozolomide and radiotherapy). CENTRIC includes patients with newly diagnosed glioblastoma and methylated O⁶-methylguanine-DNA methyltransferase (MGMT) gene promoter status. The trial was planned and is being conducted in partnership with the European Organisation for Research and Treatment of Cancer (EORTC). Detailed trial results will be submitted for presentation at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting and publication in a peer-reviewed journal.

Patient safety in CENTRIC was monitored frequently by an independent data
monitoring committee and no new or unexpected safety concerns were noted. In prior clinical studies, the most frequently reported adverse events the investigators considered to be attributed to cilengitide included nausea and fatigue.

CENTRIC is a randomized, controlled, multicenter, open-label Phase III trial. The trial evaluated the efficacy and safety of cilengitide in combination with temozolomide and radiotherapy in more than 500 patients from 23 countries worldwide with newly diagnosed glioblastoma and methylated MGMT gene promoter status. Patients whose tumors have an unmethylated MGMT gene promoter status are currently being evaluated in the Phase II, randomized, open-label, multicenter CORE^b trial.

“These results illustrate how challenging this disease remains, and that thorough
clinical investigations like in this study are crucial before adopting new treatment strategies,” said the lead investigator and president of the EORTC Professor Roger Stupp, Head of Neuro-Oncology, Department of Neurosurgery, University of Lausanne Medical Center, Lausanne, Switzerland and newly appointed director of the Zurich University Cancer Center. “Nevertheless, the unique collaboration between academia and industry was key in establishing molecular tumor characterization towards personalized medicine. And it allows for investigation of mechanisms of disease, and identifying novel targets and combinations for the future. We remain committed to addressing the needs of patients suffering from this rare disease and will continue to investigate other treatment options.”

Dr. Annalisa Jenkins, Head of Global Drug Development and Medical for Merck
Serono, commented: “The results of CENTRIC are disappointing, especially for people who are fighting this devastating and difficult to treat cancer. Over the coming months, we intend to analyze the data sets and ensure appropriate public disclosure of key information that will serve future scientific research related to targeted therapies in oncology. For a complete picture, we will also evaluate the results of the currently ongoing Phase II CORE trial, which included only patients with an unmethylated MGMT gene promoter status. We remain committed to advancing our pipeline and developing new treatment options in oncology for patients with high medical need.”

a. CENTRIC: CilENgitide in combination with Temozolomide and Radiotherapy In newly diagnosed glioblastoma Phase III randomized Clinical trial

b. CORE: Cilengitide in patients with newly diagnOsed glioblastoma multifoRme and unmethylated MGMT genE promoter

About Cilengitide
Cilengitide is the first in a new class of investigational targeted anticancer therapies – the integrin inhibitors – to have reached Phase III clinical development. Cilengitide is thought to target certain integrins overexpressed or aberrantly expressed in many cancers that are involved in tumor cell growth and the formation of new tumor-related blood vessels in the tumor microenvironment.

Cilengitide is currently being investigated in glioblastoma – a very aggressive type of brain tumor – in a Phase III trial (CENTRIC) and in a Phase II trial (CORE). An additional Phase I/II trial is ongoing in nonsmall cell lung cancer (NSCLC). Further trials are being conducted by the U.S. National Cancer Institute (NCI). In the United States and Canada, cilengitide is being developed by EMD Serono, a subsidiary of Merck.

• The CENTRIC trial is a multicenter, randomized, controlled, open-label Phase III trial in patients with newly diagnosed glioblastoma and methylated MGMT gene promoter (M+) status. The study assessed the efficacy and safety of adding cilengitide to chemoradiotherapy (CRT; temozolomide [TMZ] and radiotherapy followed by TMZ), versus CRT alone. CENTRIC was planned and conducted in close partnership with the European Organisation for Research and Treatment of Cancer (EORTC).

• The CORE trial is a multicenter, randomized, controlled, open-label Phase II trial in patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter (M–) status. The study is assessing the safety and tolerability of two cilengitide dosing schedules added to CRT, versus that of CRT alone.

About MGMT Testing
The methylation status of methylguanine-DNA methyltransferase (MGMT) gene promoter is an important molecular factor in glioblastoma tumors. MGMT is thought to contribute to cellular DNA repair. Methylation of the gene promoter in the tumor tissue silences the expression of MGMT and has been found to be a
prognostic and potentially predictive marker for benefit from temozolomide treatment in patients with newly diagnosed glioblastoma.

Merck Serono is committed to the philosophy of personalized cancer care. The clinical trial program for cilengitide includes a companion diagnostic biomarker test, PredictMDx for Glioblastoma, produced by MDx Health, which identified the methylation status of the MGMT gene in patients. Patients whose tumors
had methylated MGMT gene promoter status were included in the CENTRIC trial. Patients with unmethylated MGMT gene promoter status are currently being evaluated in the Phase II open-label multicenter CORE trial.

About EORTC
The aims of the European Organisation for Research and Treatment of Cancer (EORTC; www.eortc.org ) are to develop, conduct, coordinate, and stimulate translational and clinical research in Europe to improve the management of cancer and related problems, aiming at increasing survival but also patient quality of life. Extensive and comprehensive research in this wide field is beyond the means of individual European hospitals, and can best be accomplished through the multidisciplinary multinational efforts of basic
scientists and clinicians.

Over the past few years, numerous innovative agents have been discovered as a result of tremendous developments in the understanding of the molecular basis of cancer. Further clinical progress in cancer treatment will be accomplished mainly through the conduct of translational research projects, efficient drug
development and the execution of large, prospective, randomized, multicenter cancer clinical trials. The EORTC promotes multidisciplinary cancer research in Europe and is linked to other leading biomedical research organizations around the world.

The aim of the EORTC is to facilitate the passage of experimental discoveries into state-of-the-art treatments by keeping to a minimum the time lapse between the discovery of new anti-cancer agents and the implementation of their therapeutic benefit for patients with cancer.

The ultimate goal of the EORTC is to improve the standards of cancer treatment and care, and personalized therapy. Innovative drugs and new regimens are being evaluated, and strategies of available drug treatments, surgery and radiotherapy being optimized and combined.

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 neurodegenerative diseases, oncology and rheumatology.

About Merck
Merck is a global pharmaceutical and chemical company with total revenues of €10.3 billion in 2011, a history that began in 1668, and a future shaped by approx. 40,000 employees in 67 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

For more information, please visit www.merckserono.com or www.merckgroup.com.

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