Integrin inhibitor unable to improve overall survival in phase III trials
Merck KGaA has endured a pipeline setback with disappointing phase III results for its investigational brain cancer drug cilengitide.
The Germany-based pharma company said that cilengitide did not meet its primary endpoint of significantly increasing overall survival when added to the current standard chemoradiotherapy regimen when used in patients with newly diagnosed glioblastoma.
The news comes as a blow to Merck and its plans for what was the first integrin inhibitor to have reached phase III clinical development.
Integrin inhibitors offer a potential new way of treating cancer by targeting integrin receptors, which play a role in linking the outside of the cell with its interior.
It is thought that by inhibiting certain integrins, drugs like cilengitide can treat cancer by both targeting the tumour cells directly and inhibiting the formation of new blood vessels that carry blood to the tumour.
In line with increasing moves towards personalised cancer care, Merck's study was investigating cilengitide in patients with methylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter status.
The MGMT gene is thought to contribute to cellular DNA repair, and people with newly diagnosed glioblastoma who have methylated MGMT have been shown to benefit from current standard chemoradiotherapy treatments.
However, this has not proved the case for cilengitide in Merck's phase III CENTRIC (a) trial.
This trial was conducted in partnership with the European Organisation for Research and Treatment of Cancer (EORTC), a non-profit organisation comprising more than 300 universities that aims to support and conduct translational and clinical research in Europe.
The EORTC's president Professor Roger Stupp, head of neuro-oncology at University of Lausanne Medical Center, Lausanne, Switzerland, was lead investigator of the CENTRIC trial.
He said: “These results illustrate how challenging this disease remains, and that thorough clinical investigations like in this study are crucial before adopting new treatment strategies.
“Nevertheless, the unique collaboration between academia and industry was key in establishing molecular tumour characterisation towards personalised medicine.”
Merck said 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.
Cilengitide is also under investigation in a phase II CORE trial for use as a non-combination treatment in patients with newly diagnosed glioblastoma who have unmethylated MGMT and an additional phase I/II trial is ongoing in non-small cell lung cancer (NSCLC).