Phase 2 safusidenib erbumine mutant-IDH1 inhibitor in post-vorasidenib progressive IDH1 glioma.

Nuvation Bio’s multicenter Phase 2 study tests safusidenib erbumine (250 mg orally twice daily), a brain-penetrant small-molecule inhibitor of mutant IDH1 (including IDH1 R132) that lowers the oncometabolite 2‑hydroxyglutarate, in adults with WHO grade 2–3 IDH1-mutant glioma who progressed on vorasidenib after surgery and have not received chemo or radiation. The design is single-arm and efficacy is assessed after progression confirmed by blinded independent central review using modified RANO 2.0, with safety and tolerability as key co-objectives. The eligible population includes measurable IDH1-mutant astrocytoma and IDH1-mutant, 1p/19q-codeleted oligodendroglioma; these molecular subsets represent a large fraction of diffuse lower-grade gliomas (IDH1 mutations are common, and 1p/19q codeletion defines oligodendroglioma). The scientific/commercial angle is “sequential IDH inhibition” after vorasidenib failure—important because patients can otherwise transition to radiation plus alkylating chemotherapy (temozolomide or PCV), approaches that can control disease but carry cumulative neurocognitive and marrow toxicity risks in long-surviving populations.