A randomized, phase 3, open-label study of nivolumab versus temozolomide (TMZ) in combination with radiotherapy (RT) in adult patients (pts) with newly diagnosed, O-6-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma (GBM): CheckMate-498.

Abstract

TPS2079Background: GBM, the most common primary brain tumor in adults, has an aggressive clinical course and a median survival of 15–18 months in clinical trial populations. Approximately 40% of pts with GBM have tumors with an MGMT-methylated promoter, which is associated with sensitivity to TMZ. New treatment options for pts with GBM are desirable, particularly for those with MGMT-unmethylated GBM, as TMZ efficacy is historically marginal in this population. Nivolumab, a fully human IgG4 monoclonal antibody to the programmed death-1 receptor, has shown clinical activity and increased survival in pts with metastatic melanoma, non–small-cell lung cancer, and renal cell carcinoma. CheckMate-498 (NCT02617589) is a phase 3 study designed to compare overall survival (OS) of nivolumab or TMZ, each in combination with RT, in pts with newly diagnosed MGMT-unmethylated GBM. In a companion phase 2 trial (CheckMate-548; NCT02667587), eligible pts with MGMT-methylated tumors (N = 320) will be randomized to RT + TMZ ...