APG101, a fully human fusion protein consisting of the extracellular domain of CD95 and the Fc-domain of an IgG, has been developed by Apogenix. It was confirmed as a potent inhibitor of CD95L induced invasion of glioblastoma cells in vitro. In a randomized phase 2 study in glioblastoma patients with 1st or 2nd relapse the combined therapy of APG101 plus radiotherapy (RT) was found to be superior to RT alone in a clinically relevant order of magnitude in all efficacy endpoints (i.e. PFS-6, PFS and OS). At the same time APG101 exhibited an excellent safety profile and was well tolerated. The presented data summarizes the identification of a predictive biomarker.
To identify potential biomarkers we used available tissue sections originating from archived primary tumor of the study patients and analyzed them for the expression of CD95L as well as for the DNA methylation status.
A genome-wide assessment of DNA methylation identified a single CpG-site (CpG2) upstream of the CD95L-promotor that showed differential methylation between APG101 responders (PFS > 5 months) and non-responders (PFS
The level of CpG2 methylation in the CD95L promoter in the patients' glioblastoma tissue is a prognostic biomarker predicting response to therapy with APG101. Apogenix currently develops a qPCR-based assay to quantify CpG2 methylation. This assay is intended as companion diagnostic to identify patients that may respond best to APG101 treatment.
Clinical trial identification
Legal entity responsible for the study
M. Thiemann, C. Gieffers, C. Kunz, J. Sykora, C. Merz, H. Fricke: Employee of Apogenix AG. W. Wick: Commercial research grant from Boehringer Ingelheim and Roche; speaker's bureau honoraria from Prime Oncology; and is a consultant/advisory board member for Eli Lilly and Co. and Roche. All other authors have declared no conflicts of interest.