TIP-01. [177Lu]Lu-DOTATATE for recurrent meningioma (LUMEN-1, EORTC-2334-BTG): study protocol for a randomized phase II trial

Abstract BACKGROUND There are no established treatment options for patients with meningioma recurring after surgery and radiotherapy. Somatostatin receptor type 2 (SSTR2) is highly expressed in meningiomas and SSTR2-targeting radionuclide therapy with [177Lu]Lu-DOTATATE has shown potential activity in the treatment of pretreated and progressive meningioma in uncontrolled and small studies (Mirian et al 2021, Mair et al 2024, Merell et al 2024, Kurz et al 2024). METHODS EORTC-2334-BTG (LUMEN-1, NCT06326190) is a randomized, multicenter phase II trial for patients with pretreated recurrent meningioma of all WHO grades. A total of 136 patients will be randomized in a 2:1 ratio to [177Lu]Lu-DOTATATE (up to 4 doses 7.4 GBq given every 4 weeks) or local standard of care (hydroxyurea, bevacizumab, sunitinib, octreotide, everolimus, or observation). Main eligibility criteria include age of 18 years or above, neuropathologically confirmed meningioma of WHO CNS5 grade 1, 2 or 3, WHO performance score 0-2, measurable disease on MRI (≥ 10 x 10 mm), radiologically documented progression of any existing tumor (growth >25% or new lesions) or appearance of new lesions within the last two years, SSTR positivity by PET imaging (SUVmax >2.3), at least one prior surgery and at least one line of radiotherapy, and no prior systemic therapy. The primary efficacy endpoint is locally assessed progression-free survival (PFS) according to RANO MRI meningioma criteria. Secondary endpoints include radiological response rate, overall survival, safety, health-related quality of life, and neurological function. The trial protocol includes a comprehensive exploratory translational research program including dosimetry, imaging-based, and tissue-based investigations. LUMEN-1 was activated on March 10th 2025 and will enroll patients in 35 sites in 10 countries across Europe with primary endpoint collection planned after two years and study completion after 5 years. CONCLUSION EORTC-2334-BTG (LUMEN-1, NCT06326190) is the first prospective randomized trial investigating the efficacy of [177Lu]Lu-DOTATATE in patients with recurrent meningioma.