INNV-01. Combination lutetium Lu 177 dotatate for refractory meningioma

Abstract No effective therapy exists for recurrent meningioma beyond surgery and radiation therapy. Numerous therapeutic approaches for recurrent meningiomas have been futile. Actionable targets exist, but these driver mutations vary across meningiomas and may be absent entirely. Accordingly, somatostatin receptor (SSTR) analogs are an attractive therapeutic given the ubiquitous expression of SSTR2 in nearly all meningiomas. This high expression profile provides the advantage of a universal targeted therapy that can treat nearly the entire cohort of meningiomas. For these reasons, somatostatin analogs, including octreotide, have garnered considerable interest. Though octreotide carries high affinity to SSTR, octreotide monotherapy in meningiomas has been met with marginal success. These failures have been attributed to intracellular escape mechanisms, leading to the emergence of SSTR-targeted therapeutics with mechanisms independent of intracellular signaling, such as lutetium Lu-177 dotatate (Lu-177), a peptide receptor radionuclide therapy (PRRT). However, results with Lu-177 as a monotherapy in recurrent meningioma have been suboptimal. Accordingly, multi-SSTR-targeted therapy utilizing mechanisms both dependent and independent of intracellular pathways may overcome the escape mechanisms associated with either octreotide or Lu-177. The superiority of this combinatorial therapy compared to octreotide alone was proven in the NETTER trials and gained regulatory approval for advanced SSTR-positive gastroenteropancreatic neuroendocrine tumors. The success of this study will broaden the treatment options for refractory meningiomas. SSTR represents a universal target that is collectively found in nearly all meningiomas. This commonality is an integral component for practice-changing initiatives that are cost-effective, generalizable, scalable and favorable to real-world adoption. This distinguishing feature diverges from other targeted approaches for meningiomas, which are reliant on specific driver mutations, which occur in lower frequency in which these individual mutations occur (NF2 43-55%, SMO 3-5%, PIK3 4.5%, AKT1 9%). We present two cases of patients with refractory meningioma treated with combination Lutathera and octreotide.