TIP-05. Regorafenib versus local standard of care in patients with grade 2-3 meningioma no longer eligible for loco-regional treatments: the MIRAGE trial

Abstract BACKGROUND Meningiomas are the most common intracranial tumors. The role of systemic treatments remains poorly supported by evidence. Regorafenib is an oral multi-tyrosine kinase (RTK) inhibitor with high selectivity for VEGFR1/2/3. It also inhibits PDGFRβ, FGFR1, c-RAF/RAF1 and BRAF pathways, highly expressed in high-grade meningiomas. METHODS The MIRAGE Trial (NCT06275919) is a multicenter, open-label, randomized phase 2 clinical trial evaluating grade 2/3 meningioma pts progressed following surgery and radiotherapy. A total of 94pts are being randomized (1:1) to receive either regorafenib (160mg orally for 3 weeks-on, 1 week-off) or local standard-of-care therapies (e.g., bevacizumab, hydroxyurea, somatostatin analogues). Major inclusion criteria include histological confirmation of WHO2021 grade 2-3 meningioma, radiological progression at least 24weeks from radiotherapy (estimated planar growth >25% in two dimensional tumor areas within the prior 12ms or development of a new lesion) with at least 1 measurable lesion (minimum 10x10mm) on baseline MRI, ineligibility for further surgery and/or radiotherapy, absence of extracranial lesions and a WHO PS 0-1. The primary endpoint is 6m-PFS. Assuming a 6m-PFS of 20% in the control arm and 40% in the regorafenib arm (corresponding to a HR=0.57) with a=5%, b=85%, 104 pts are needed to assess the targeted efficacy. Response to treatment will be assessed per RANO criteria. Secondary endpoints include OS, ORR, DCR, volumetric analysis of the target lesions, safety and QoL. Multi-omics and radiomics exploratory analyses will also be performed. MIRAGE, initiated in Sep2024, is an academic trial promoted by the Istituto Oncologico Veneto and will recruit patients across 15 neuro-oncology Centers in Italy with an estimated study duration of 18ms. To date, 20pts have been enrolled. DISCUSSION MIRAGE is the first randomized phase 2 trial analyzing the role of a RTK inhibitor (regorafenib) in prolonging PFS in pts with grade 2-3 meningioma ineligible for further surgery and/or radiotherapy.