10199-CS-20 IDH-mutant glioma patients treated with Vorasidenib: rationale, design and trial in progress of the Vorasidenib Expanded Trial in Japan

Abstract Background Vorasidenib (VOR) is an oral, brain-penetrant, dual inhibitor of isocitrate dehydrogenase 1/2 mutations (mIDH1/2) that demonstrated clinical efficacy and safety in patients with mIDH1/2 glioma in the phase 3 INDIGO study (NCT04164901), which included a Japanese cohort with 16 patients. VOR is currently registered in seven countries; however, more than 2300 patients across 19 countries have already received treatment through Managed Access Programs. To provide early access to VOR in Japan and demonstrate its safety and tolerability, Servier opened an Expanded Trial (ET) (jRCT2061250027) in July 2025 under the national “Kakudai-Chiken” scheme. Methods This prospective, multicenter, open-label trial is planned to enroll >96 eligible Japanese participants aged >12 years with mIDH1/2 glioma who have undergone surgery, including biopsy, as their only treatment. VOR 40 mg will be administered daily, the same dosage as in the INDIGO study, and visits, including safety assessments, will occur monthly for the duration of treatment, as long as the patient continues to receive benefit. Key data captured in the trial will include demographics, baseline disease characteristics, and safety/tolerability. Patients will be enrolled over a period of 6 months at each of the eight centers that participated in the INDIGO study. Following the submission of a New Drug Application to the Pharmaceuticals and Medical Devices Agency (PMDA) for VOR in mIDH1/2 glioma in December 2024, the ET is designed to transition seamlessly to treatment availability through physician prescription, ensuring treatment continuity. Results/Outlook With the first patient enrolled in July 2025, baseline characteristics and safety findings of the VOR expanded trial are expected in December 2026.