Lutetium Lu177 Edotreotide (ITM-11): A Comprehensive Monograph on a Novel Radiopharmaceutical for Neuroendocrine Tumors

Executive Summary

Lutetium Lu177 Edotreotide, also known by the development code ITM-11, is an investigational, small-molecule radiopharmaceutical agent representing a significant advancement in the field of peptide receptor radionuclide therapy (PRRT). It is designed for the targeted treatment of somatostatin receptor-positive (SSTR+) neuroendocrine tumors (NETs), a heterogeneous group of malignancies for which therapeutic options remain limited. The drug is a complex radioconjugate, composed of the somatostatin analogue edotreotide (DOTATOC), the chelator DOTA, and the therapeutic beta-emitting radioisotope Lutetium-177 (177Lu). Its mechanism of action relies on the high-affinity binding of edotreotide to SSTRs, particularly subtype 2, which are densely expressed on the surface of many NET cells. Following binding, the agent is internalized, delivering a highly localized and cytotoxic dose of radiation that induces DNA damage and subsequent tumor cell apoptosis.

The clinical development of Lutetium Lu177 Edotreotide is spearheaded by two pivotal Phase III trials. The recently completed COMPETE trial (NCT03049189) evaluated its efficacy and safety in patients with Grade 1 and 2 gastroenteropancreatic NETs (GEP-NETs) against the approved standard-of-care mTOR inhibitor, everolimus. The trial successfully met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). Patients treated with Lutetium Lu177 Edotreotide experienced a median PFS of 23.9 months compared to 14.1 months for those receiving everolimus. Furthermore, the drug exhibited a favorable safety profile, with a lower incidence of treatment-related adverse events compared to the active comparator.