Merck KGaA: 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, February 25, 2013 – Merck KGaA of
Darmstadt, Germany, announced today that the Phase III CENTRICa
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 COREb 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,”
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 the Merck KGaA, Darmstadt, Germany, prescription
medicines division, 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 genepromoter 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
b - CORE: Cilengitide in patients with newly diagnOsed glioblastoma multifoRme and unmethylated MGMT genE promoter
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 over-expressed 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 non-small 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 KGaA,
?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
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 KGaA of Darmstadt, Germany, 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.
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
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About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, 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 KGaA's operating
activities come under the umbrella of Merck KGaA, Darmstadt,
Germany, 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.
Worldwide there are two separate companies that bear the name “Merck”, the original Merck KGaA from Darmstadt, Germany, the oldest pharmaceutical and chemical company in the world, and the pharmaceutical company Merck & Co. in the United States. The rights to the name and trademark MERCK in North America (USA and Canada) lie with Merck & Co., the former U.S. subsidiary of Merck, whereas Merck KGaA operates in North America under the umbrella brand EMD. In the rest of the world, Merck KGaA owns the rights to the Merck name and trademark. This press release was distributed by Merck KGaA, Darmstadt, Germany.
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Posted: February 2013