DDDR-49. IGF1R inhibition arrests meningioma growth

Abstract Meningiomas are the most common primary tumors of the central nervous system. While standard-of-care treatment—surgical resection and/or radiotherapy—is effective for most patients, a subset of tumors progress despite these interventions. To identify novel therapeutic targets, we generated single-cell transcriptomic atlases of WHO grade 1 and 2 meningiomas. This analysis revealed multiple tumor cell states and highlighted robust activation of the Insulin-like Growth Factor 2–Insulin-like Growth Factor 1 Receptor (IGF2–IGF1R) signaling axis, a key regulator of cell metabolism and growth. Inhibition of IGF1R in fresh patient-derived 2D cultures and ex vivo explant models suppressed tumor cell proliferation. Based on these findings, a patient with a rapidly progressing, IGF2–IGF1R–expressing grade 2 meningioma—previously treated with radiotherapy—was administered Ceritinib, an IGF1R inhibitor. While the tumor had been growing at a rate exceeding 1 mm/month prior to treatment, no further growth was observed after two months of Ceritinib therapy. In summary, we identified IGF2–IGF1R signaling as an active and targetable pathway in meningioma. Ceritinib demonstrated both preclinical efficacy and promising early clinical activity in a case of radiotherapy-resistant recurrent meningioma. To our knowledge, this represents the first report of clinical efficacy of Ceritinib in meningioma.