CTNI-53. PATIENTS WITH ISOCITRATE DEHYDROGENASE-MUTANT GLIOMA TREATED WITH VORASIDENIB: UPDATED DATA FROM THE VORASIDENIB EXPANDED ACCESS PROGRAM

Abstract BACKGROUND Vorasidenib (VOR) is an inhibitor of mutant isocitrate dehydrogenase 1/2 (mIDH1/2). We previously reported outcomes from an expanded access program (EAP; NCT05592743) providing VOR to people with mIDH1/2 glioma. Enrollment closed after FDA approval (August 2024); participants then transitioned off the program. Here, we describe the EAP population to highlight real-world use of VOR. METHODS Eligible participants were aged ≥12 years with mIDH1/2 glioma who, per their treating oncologist, would potentially benefit from VOR. Safety assessments occurred every 2 weeks for the first two 28-day cycles, and monthly thereafter. RESULTS As of April 30, 2025, 153 participants (median age, 39 [range: 12–83] years; 84 [54.9%] male) had entered the EAP. Eighty-two (53.6%) had astrocytoma, 115 (75.2%) had grade 2 tumors, 119 (77.8%) had mIDH1 tumors, and 87 (56.9%) had undergone subtotal resection or biopsy. Most (n=85 [55.6%]) had ≥1 prior systemic treatment(s), including radiation ± chemotherapy (n=54), IDH inhibitors (n=35), chemotherapy only (n=11), and vaccine (n=1). At program closure, 124 (81.0%) participants were receiving VOR, 26 (17.0%) had discontinued VOR (disease progression, n=19; adverse events [AEs], n=2; other, n=6), and 3 (2.0%) had died (disease progression, n=2; unrelated infection, n=1). Median (range) durations of treatment were 220 (2–762) days in the overall population, 220 (11–762) and 209 (2–540) days, respectively, in participants with grade 2 and 3 gliomas, and 221.5 (11–762) days in participants with progressive/recurrent disease at initiation. Forty-eight (31.4%) participants had ≥1 AE (any grade), 5 (3.3%) had serious AEs, 11 (7.2%) had AEs of special interest (≥grade 2 ALT/AST elevations). CONCLUSIONS These data provide additional insight into the real-world use and safety of VOR in a heterogeneous population that, in contrast to the Phase 3 INDIGO study, included patients with grade ≥3 tumors, prior systemic treatment, and was enriched for mIDH2.