Phase III Trial Comparing 177Lu-Edotreotide with Standard Care for GEP-NETs (Grades 2 and 3)

Gastroenteropancreatic (GEP-NET_s) account for approximately 70% of neuroendocrine tumors. Patients with this condition often experience the development of metastatic disease, which presents with limited therapeutic interventions. The treatment options for well-differentiated high-grade 2 and 3 gastroenteropancreatic neuroendocrine tumors (GEP-NET_s) comprise peptide receptor radionuclide therapy (PRRT), somatostatin analogs, chemotherapy, cytoreduction, and molecularly targeted therapies such as everolimus and sunitinib. The order of administration of these therapies has not been specified. The PRRT procedure involves the utilization of radiolabelled somatostatin analogs that specifically target tumor cells expressing somatostatin receptors (SSTR+). The utilization of the aforementioned treatment may stabilize the disease and elicit an objective response in the tumor. The radiolabelled somatostatin analog known as¹⁷⁷Lu-edotreotide exhibits promising efficacy and a favorable safety profile, making it an innovative option in the field. The retrospective data about metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NET_s) treated with two or more cycles of¹⁷⁷ Lu-edotreotide indicates a progression-free survival (PFS) of at least 30 months. The ongoing phase III COMPETE trial is currently evaluating the efficacy and safety of¹⁷⁷ Lu-edotreotide in comparison to everolimus for the treatment of grade 1 and 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET_s).

The COMPOSE study is a phase III clinical trial currently enrolling patients with well-differentiated aggressive grades 2 and 3 (Ki-67 index 15−55%), SSTR+, and GEP-NETs. This is a prospective, randomized, controlled, open-label, multicenter trial. The study aims to assess the effectiveness, safety, and patient-reported outcomes of ¹⁷⁷Lu-edotreotide PRRT as a first or second-line treatment option compared to the best standard of care, which may include chemotherapy (CAPTEM or FOLFOX) or everolimus. The COMPOSE study endeavors to conduct a randomized trial of 202 patients, with a 1:1 allocation ratio, to receive a specific number of cycles of ¹⁷⁷ Lu-edotreotide or the comparator. The primary endpoint of this study is progression-free survival (PFS), which will be evaluated every 12 weeks until the occurrence of disease progression (as per RECIST v1.1) or death, whichever comes first. The secondary endpoints comprise the evaluation of the overall survival rate, which will be conducted up to two years following the onset of disease progression. Recruitment is underway at 14 sites in various countries, such as Australia, France, Spain, Sweden, the United Kingdom, and the United States. Additional locations and nations will likely adopt similar measures. Anticipated outcomes are poised to expand therapeutic alternatives for individuals diagnosed with well-differentiated aggressive grade 2 and 3 gastroenteropancreatic neuroendocrine tumors (GEP-NET_s), encompassing initial treatment options.

Source: https://oncologypro.esmo.org/meeting-resources/esmo-congress/compose-pivotal-phase-iii-trial-to-compare-177lu-edotreotide-with-best-standard-of-care-for-well-differentiated-aggressive-grade-2-and-grade-3-gas

Clinical Trail: https://clinicaltrials.gov/ct2/show/NCT04919226

T.R. Halfdanarson, D. Halperin, D. Reidy-Lagunes, G. Kong, J. Mailman, K. Herrmann, R. Sri Rajaskanthan, S. LEYDEN, J. Capdevila Castillon, C. Sierras, P. Harris/ 902TiP – COMPOSE: Pivotal phase III trial to compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors/Annals of Oncology (2022) 33 (suppl_7): S410-S416. 10.1016/annonc/annonc1060