CTNI-09. VORASIDENIB AS MAINTENANCE TREATMENT AFTER FIRST-LINE CHEMORADIOTHERAPY IN IDH-MUTANT GRADE 2/3 ASTROCYTOMA: STUDY PROTOCOL FOR THE PLACEBO-CONTROLLED, TRIPLE-BLIND, RANDOMIZED PHASE III STUDY EORTC-2427 (VIGOR)

Abstract BACKGROUND The efficacy of vorasidenib as maintenance therapy after completion of standard of care remains unclear. The VIGOR trial will investigate the efficacy of adding vorasidenib as maintenance therapy after completion of standard radiochemotherapy in patients with astrocytoma, IDH-mutant, WHO grade 2 or 3. MATERIAL AND METHODS VIGOR is a comparative, randomized (1:1), triple-blinded, multicentre phase III superiority trial. A total of 468 adult patients with an astrocytoma, IDH-mutant, WHO grade 2 or 3, at least one prior neurosurgery, who were in need for radiochemotherapy and completed standard of care radiotherapy followed by chemotherapy will be randomized between placebo or vorasidenib monotherapy 40 mg once daily until disease progression, unacceptable toxicity, or withdrawal of patient consent for up to 5 years. The primary objective is to demonstrate that vorasidenib maintenance therapy improves locally assessed PFS from enrolment compared to placebo. Primary endpoint is PFS from randomization, patients are randomized upon completion of the adjuvant chemotherapy. Secondary endpoints include PFS from start of radiotherapy, overall survival, time to next intervention, toxicity, health related quality of life, neurological symptoms and neurocognitive function. Translational research including tissue samples, liquid biopsies, and neuroimaging data is planned. Patients will be enrolled in 10 European countries (European Organisation for Research and Treatment of Cancer (EORTC) sites), Australia (Cooperative Trials Group for Neuro-Oncology (COGNO) sites) and Canada (Canadian Cancer Trials Group (CCTG) sites). Trial activation is planned for December 2025. The inclusion duration is 3 years, total study duration is approximately 130 months (10.8 years). CONCLUSION VIGOR (EORTC-2427-BTG) will investigate the efficacy and safety of adding maintenance vorasidenib after completion of radiochemotherapy in patients with newly diagnosed astrocytoma, IDH-mutant, WHO grade 2 or 3. If the trial is positive, this has the potential to become a new standard of care. CLINICAL TRIAL REGISTRATION 2024-519404-27-00 (EudraCT-number). FUNDING Servier.