10312- ACT-20 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): JAPAN SUBGROUP ANALYSIS

Abstract INTRODUCTION The Phase 3 INDIGO study (NCT04164901) evaluated vorasidenib, an oral, brain-penetrant, dual inhibitor of mutated isocitrate dehydrogenase 1/2 (mIDH1/2), in patients with mIDH1/2 diffuse glioma. 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. In March 2023, the study was unblinded following committee recommendation. We present results for patients from Japan. METHODS Patients with grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (aged ≥12 years; Karnofsky Performance Status, ≥80; measurable non-enhancing disease; surgery as only prior treatment; no immediate need of chemoradiotherapy). Patients were randomized 1:1 to vorasidenib 40 mg or placebo daily in 28-day cycles. RESULTS In Japan, nine patients were randomized to placebo and seven to vorasidenib. At unblinding, all patients receiving placebo crossed over to vorasidenib. Study unblinding occurred in close succession to enrollment in Japan resulting in a short duration of placebo exposure. The Japan subgroup included all patients who received ≥1 dose of vorasidenib (n=16; median age, 44.0 years; oligodendroglioma, 10; astrocytoma: 6). As of March 2024, mean (SD) duration of vorasidenib exposure was 10.2 (3.0) months and 81.3% remained on treatment. No progression events per BIRC or deaths occurred. Median PFS and TTNI were not estimable: one patient received anticancer therapy and no other TTNI events occurred. All-grade adverse events occurring in >20% patients were increased alanine transferase (68.8%, Grade≥3: 25.0%), increased aspartate aminotransferase (56.3%; Grade≥3: 18.8%) and increased gamma-glutamyltransferase (31.3%, Grade≥3: 6.3%). CONCLUSIONS Vorasidenib is an effective targeted therapy for patients with mIDH1/2 diffuse glioma in this Japanese patient population. Findings are consistent with the statistically significant and clinically meaningful benefit of vorasidenib in the overall INDIGO study population.