10197-CS-19 A global, randomized, double-blinded, Phase 3 study of Vorasidenib versus placebo in patients with adult-type diffuse glioma with an IDH1/2 mutation (INDIGO): updated data from the Japan subgroup analysis

Abstract Introduction Vorasidenib is an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2). The Phase 3 INDIGO study (NCT04164901) evaluated vorasidenib in patients with mIDH1/2 diffuse glioma. After the primary endpoint of progression-free survival (PFS) per blinded independent review committee (BIRC) and key secondary endpoint of time to next intervention (TTNI) were met in the second interim analysis, the study was unblinded following committee recommendation. Herein, we present updated results for patients from Japan. Methods Patients with Grade 2 mIDH1/2 oligodendroglioma or astrocytoma (aged >12 years; Karnofsky Performance Status, >80; measurable non-enhancing disease; surgery as only prior treatment; no immediate need of chemoradiotherapy) were randomized 1:1 to vorasidenib 40 mg or placebo daily in 28-day cycles. After unblinding, all patients receiving placebo were able to transfer to vorasidenib. Results In Japan, 16 patients were randomized in INDIGO (placebo, n = 9; vorasidenib, n = 7), but study unblinding and crossover to vorasidenib occurred shortly after enrollment was completed, resulting in a short exposure to placebo. As of February 2025, median follow-up was 22.6 months (95% CI, 22.2, 23.5). All patients from Japan had received more than 1 dose of vorasidenib (oligodendroglioma, n = 10; astrocytoma, n = 6; median age, 44. 0 years) and 11 (68.3%) remained on treatment. Overall, four (25.0%) progression events per BIRC occurred and median PFS was not estimable (NE; 95% CI, 19.3, NE). Three (18.8%) patients were censored from the PFS analysis as they had started a subsequent anticancer therapy. No new safety signals emerged; updated safety data will be presented. Conclusions Vorasidenib is an effective targeted therapy for patients with mIDH1/2 diffuse glioma in this Japanese patient population. Findings of this subgroup analysis remain consistent with the statistically significant and clinically meaningful benefit of vorasidenib in the overall INDIGO study population.