Current status of phase III anti-EGF-receptor antibody (OSAG-101) for newly diagnosed glioblastoma.

Abstract

2056 Background: EGF-R is the most consistently expressed cell surface marker for glioblastoma. Therapies are directed against the intercellular signalling pathway or the cell surface binding of the cognate ligands. Because of the selectivity of this molecule for gliomas and promising preclinical and early clinical findings, to evaluate the therapeutic effect of a monoclonal antibody (nimotuzumab) which has a lower affinity than cetuximab, thus binding more specifically to highly overexpressing cells is warranted in a phase III design. Methods: Nimotuzumab (OSAG-101) is tested in an open label, randomized, multicenter phase III trial in patients with newly diagnosed glioblastoma. OSAG-101 is administered by i.v. infusion (weekly infusion of 400 mg) on top of the current standard radiochemotherapy with temozolamide followed by biweekly infusions of 400 mg thereafter until progression. Patients with histologically confirmed glioblastoma were included without specification of resection status. Patients under the age of 18 and over 70 years were excluded. Primary endpoint was time to progression as determined by centralized neuro-imaging review using a standardized evaluation protocol. Overall survival serves as a secondary endpoint with quality of life and safety as additional parameters. Results: Between August 2008 and December 2009, 130 patients were enrolled in 10 sites with 150 subjects. All except one patient were GBM on central histopathological review. 60 patients had a gross total resection with no residual contrast enhancement and 70 patients had partial resections with residual contrast enhancement, including patients with biopsy only. The observed adverse reaction pattern was the same in both study arms and both strata and reflecting the event pattern of the disease and its standard treatment. No rash, conjunctivitis or mucositis were reported. Conclusions: The intravenous administration of OSAG-101 for newly diagnosed glioblastoma is safe and free of additional toxicity to the standard radiochemotherapy regimen. With 75 patients just having reached their primary endpoint, an interim analysis will be available by march 2010. Accrual is expected to be complete by April 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Oncoscience