Pivotal phase III COMPOSE trial will compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors.

TPS514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which represent approximately 70% of NETs, frequently develop metastatic disease with limited treatment options. Current standard therapies for well-differentiated high grade 2 and grade 3 GEP-NETs include cytoreductive procedures, somatostatin analogues, molecular targeted therapies (everolimus or sunitinib), chemotherapy and peptide receptor radionuclide therapy (PRRT), with no specified sequence of use. PRRT may stabilize disease and induce objective tumor responses. This treatment uses radiolabeled somatostatin analogues to selectively target somatostatin receptor expressing (SSTR+) tumor cells. 177 Lu-edotreotide is an innovative radiolabeled somatostatin analogue with a favorable safety profile and promising efficacy. Retrospective data in metastatic GEP-NETs treated with two or more 177 Lu-edotreotide cycles demonstrated a progression free survival (PFS) of at least 30 months. The currently recruiting Phase III COMPETE trial compares the efficacy and safety of 177 Lu-edotreotide, versus everolimus, in grade 1 and grade 2 GEP-NETs. Methods: COMPOSE (NCT04919226) is a prospective, randomized, controlled, open-label, multi-center Phase III study, in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15−55%), SSTR+, GEP-NETs. This trial is to evaluate the efficacy, safety and patient-reported outcomes of first- or second-line treatment with 177 Lu-edotreotide PRRT compared to best standard of care. It aims to randomize 202 patients 1:1 to a defined number of cycles of 177 Lu-edotreotide or an active comparator (either chemotherapy [CAPTEM or FOLFOX] or everolimus, according to investigator´s choice). The primary endpoint is PFS, assessed every 12 weeks until disease progression (RECIST v1.1), or death, whichever occurs earlier. Secondary outcomes include overall survival, assessed up to 2 years after disease progression. Study recruitment for COMPOSE commenced in September 2021. It is expected that COMPOSE will inform optimal treatment options for patients with well-differentiated high grade 2 and grade 3 SSTR+ GEP-NETs, including for first-line therapy. Clinical trial information: NCT04919226.