Vorasidenib (dual mutant IDH1/2 inhibitor) delivers ~50-month PFS and delays next intervention in grade 2 IDH-mutant glioma

Vorasidenib (VOR) is an oral, brain-penetrant dual inhibitor of mutant IDH1/2, evaluated in the global, randomized, double-blind Phase 3 INDIGO trial (NCT04164901) in residual/recurrent grade 2 IDH1/2-mutant oligodendroglioma or astrocytoma after surgery only (no prior RT/chemo; no immediate need for chemoradiotherapy), with 331 patients randomized (VOR n=168; placebo n=163). With updated follow-up to January 17, 2025 among patients randomized to VOR (median follow-up 41.6 months), investigator-assessed median PFS was 49.9 months (95% CI 39.6–NE) and median time to next intervention (TTNI) was not reached (95% CI 52.0–NE); at 42 months, 59.2% were progression-free and 75.1% had not yet required chemoradiotherapy or surgery, with ORR 31.5% (95% CI 24.6–39.2) and OS not reached. Versus the original INDIGO blinded comparison (BIRC) at earlier cutoff—median PFS 27.7 vs 11.1 months (HR 0.39) and delayed TTNI with placebo crossover allowed—this update mainly reinforces durability on continuous VOR; safety was consistent with prior reports with no new safety signals (but updated Grade ≥3 AE rates/discontinuations were not provided in the abstract for benchmarking).