Phase 2 study to evaluate the clinical efficacy and safety of MEDI4736 (durvalumab) in patients with glioblastoma (GBM).

Abstract

TPS2080Background: Outcome among newly diagnosed and recurrent GBM patients remains poor, and novel therapeutic approaches are needed. Blockade of Programmed death-1 (PD-1) and PD-ligand 1 (PD-L1) has shown promising clinical benefit among solid tumors, and data implicate PD-1/PD-L1 signaling as a significant contributor to immunosuppression in GBM. Specifically, PD-1 is expressed by many GBM infiltrating lymphocytes, PD-L1 is expressed by 61-100% of GBM tumors, and loss of the PTEN tumor suppressor gene, occurring in 40-50% of GBM tumors, leads to increased transcription and expression of PD-L1. Durvalumab (DUR) is a human IgG1 mAb against PD-L1. Bevacizumab (BEV) is a mAb against VEGF, and data suggest that VEGF inhibition may enhance the antitumor benefit of immunotherapies. Methods: This ongoing Phase 2, multicenter, open-label study (NCT02336165) is designed to evaluate the clinical efficacy and safety of DUR (10 mg/kg i.v. Q2W for 12 months) in 5 cohorts of newly diagnosed and recurrent GBM patients...