Another active area of investigation is the use of targeted agents in place of TMZ, While trials replacing TMZ with targeted agents in unselected patients without MGMT promoter hypermethylation have also shown no OS benefit, an important new Phase 1/11a NCT Neuro Master Match umbrella trial is ongoing in newly diagnosed glioblastoma patients with IDH-wild type, without MGMT promoter hypermethylation, with a variety of promising agents in combination with standard radiation therapy (113). Here, IDH2 is linked to glioblastoma.