Merck Serono, a division of Merck, Darmstadt, Germany, has announced 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 randomised, controlled, multicentre, 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 tumours have an unmethylated MGMT gene promoter status are currently being evaluated in the Phase II, randomised, open-label, multicentre 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 tumour characterisation towards personalised 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 analyse 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 randomised Clinical trial
(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 tumour cell growth and the formation of new tumour-related blood vessels in the tumour microenvironment.
Cilengitide is currently being investigated in glioblastoma – a very aggressive type of brain tumour – 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 US National Cancer Institute (NCI). In the US and Canada, cilengitide is being developed by EMD Serono, a subsidiary of Merck.
- The CENTRIC trial is a multicentre, randomised, 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 multicentre, randomised, 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.