Fig. 2.

Example of a next generation phase II/III clinical trial for newly diagnosed GB. Patients are randomized after stratification by presence or absence of MGMT promoter methylation (MGMT), clinical factors (recursive partitioning analysis or RPA), and molecular features (gene expression profile or MCP). All patients receive standard temozolomide (TMZ) chemotherapy on days 1 to 42 during radiotherapy and on days 1 to 5 of 28-day cycles during adjuvant treatment. Patients will also receive a combination of placebo, ipilimumab (Ipi), or nivolumab (Nivo) in four treatment arms. A “pick the winner” trial design will be used during phase II to move the most efficacious treatment arm forward into a larger phase III clinical trial. A combination of OS, treatment-related toxicity, neurocognitive function (NCF), and symptom burden will be used to pick the best treatment (arms). Figure was created for this manuscript by the authors