A phase 2 trial of TRC105 with bevacizumab for bevacizumab refractory glioblastoma.

2035Background: Endoglin is an endothelial cell membrane receptor highly expressed on tumor vessels that is essential for angiogenesis. It is upregulated by hypoxia and VEGF inhibition and may be an important mechanism of VEGF resistance. The combination of TRC105, an anti-endoglin monoclonal antibody, in combination with bevacizumab (Bev) has demonstrated activity in Bev refractory cancer patients with non-CNS tumors. We hypothesized that TRC105 administered with Bev would improve overall survival in glioblastoma patients who progressed on Bev. Methods: Patients with previously treated, recurrent glioblastoma (GBM) with radiographic progression following Bev therapy, KP status ≥ 70%, and adequate organ function were treated with TRC105 10 mg/kg weekly as a single agent (six patients) and then in combination with Bev 10 mg/kg every two weeks (16 patients). The primary endpoint for treatment with TRC105 and Bev was overall survival (OS), with the null hypothesis being OS of 4.0 months and alternative hypot...