Merck's Cilengitide Fails to Meet Primary Endpoint in Phase III Trial

Merck’s investigational integrin inhibitor cilengitide did not meet its primary endpoint in the CENTRIC Phase III trial evaluating if the agent could prolong overall survival when added to the current standard chemoradiotherapy regimen (temozolomide and radiotherapy). The randomized, controlled, multicenter, open-label trial, conducted in partnership with the European Organisation for Research and Treatment of Cancer (EORTC), assessed the safety and efficacy of cilengitide treatment in more than 500 patients with newly diagnosed glioblastoma and methylated-methylguanine-DNA methyltransferase (MGMT) gene promoter status from 23 countries worldwide. The results of the trial will be presented at the American Society of Clinical Oncology (ASCO) 2013 Annual Meeting and submitted for publication in a peer-reviewed journal.

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

“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 in a press statement. “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.”

In the same statement, Dr. Annalisa Jenkins, head of global drug development and medical for Merck, 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.”

Merck is developing cilengitide as an anticancer therapy. The agent 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 evaluated for the treatment of glioblastoma in a Phase III trial (CENTRIC) and in a Phase II trial (CORE). An additional Phase I/II trial is ongoing in patients with non-small cell lung cancer (NSCLC). Further trials are being conducted by the US National Cancer Institute (NCI).