CTNI-53. 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 EFFICACY RESULTS

作者：Ingo K. Mellinghoff, Martin J. van den Bent, Mehdi Touat, Deborah T. Blumenthal, Katherine B. Peters, Benjamin M. Ellingson, Jennifer Clarke, Joe Mendez, Shlomit Yust‐Katz, Warren Mason, François Ducray, Yoshie Umemura, Burt Nabors, Andreas F. Hottinger, Yoshiki Arakawa, Juan Manuel Sepúlveda-Sánchez, Wolfgang Wick, Riccardo Soffietti, James Perry, Pierre Giglio, Macarena de la Fuente, Elizabeth A. Maher, Adriana E. Tron, Dan Zhao, Shuchi S. Pandya, Lori Steelman, Islam Hassan, Patrick Y. Wen, Timothy F. Cloughesy · 发表于：Neuro-Oncology · 年份：2024 · DOI：10.1093/neuonc/noae165.0420 · 被引用次数：7 · 研究领域：Glioma Diagnosis and Treatment、Cancer Mechanisms and Therapy、Lung Cancer Treatments and Mutations

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 positive, preplanned second interim analysis (IA2). The study was unblinded in March 2023 following independent data monitoring committee recommendation. Here, we present results after an additional 6 months of follow-up between the database lock for IA2 (September 6, 2022) and study unblinding (March 7, 2023). METHODS Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (≥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 Overall, 331 patients were randomized (median age: 40.0 years; oligodendroglioma: 172; astrocytoma: 159). As of March 7, 2023, 123/168 (73%) patients remained on vorasidenib and 72/163 (44%) remained on placebo. PFS per BIRC remained in favor of vorasidenib (HR, 0.35; 95% CI, 0.25–0.49), and was consistent with PFS per investigator assessment (HR, 0.34; 95% CI, 0.23–0.50). Median PFS per BIRC: vorasidenib, not estimable (NE; 95% C...