N.c.a. 177Lu-Edotreotide is known as an innovative Targeted Radionuclide Therapy agent with favorable safety profile and promising efficacy. N.c.a. 177Lu-Edotreotide received an Orphan Designation as treatment of gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) based on academic clinical Phase II data suggesting a significant benefit (substantially improved progression-free survival, PFS). In 2017, a phase III clinical trial – known as COMPETE – with Solucin® as IMP was started. COMPETE is an international pivotal multi-center phase III clinical trial evaluating the efficacy and safety of n.c.a.177Lu-Edotreotide (Solucin®) compared to Everolimus in patients with inoperable, progressive, somatostatin-receptor positive neuroendocrine tumors of gastroenteric or pancreatic origin (GEP-NET).
N.c.a. 177Lu-Edotreotide consists of two molecular components. Firstly, there is Edotreotide, an octreotide-derived Somatostatin analogue, and secondly, n.c.a. Lutetium-177, a synthetic, low-energy beta-emitting isotope of Lutetium (EndolucinBeta®).
Edotreotide contains DOTA, which functions as a chelator for radioisotopes, and TOC, a synthetic Somatostatin receptor ligand. The compound Edotreotide binds with high affinity to Somatostatin receptors and retains both its receptor binding properties and its physiological function when labeled with 177Lu. Somatostatin receptors are predominantly overexpressed by neuroendocrine tumors. 177Lu-Edotreotide, upon binding to Somastotatin receptors in vivo is internalized and retained by tumor cells. Upon decay, the isotope emits cytotoxic medium-energy beta particles of ≤ 1.7 mm path length in soft tissue.
Compared to 90Y-Edotreotide, 177Lu-Edotreotide Targeted Radionuclide Therapy in NET was found to be less haematotoxic and associated with a longer median overall survival. That was highly significant for patients with low tumor uptake as well as for patients with extra hepatic and solitary metastases. In a retrospective Phase II trial 177Lu-Edotreotide showed a low uptake/dose delivered to normal organs and a very high tumor-to-kidney ratio.