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 tumours

Background

Approximately 70% of neuroendocrine tumours are gastroenteropancreatic (GEP-NETs). These frequently develop metastatic disease with limited treatment options. For well-differentiated high grade 2 and 3 GEP-NETs, current therapies include peptide receptor radionuclide therapy (PRRT), somatostatin analogues, chemotherapy, cytoreduction and molecular targeted therapies (everolimus, sunitinib) with no specified use sequence. PRRT uses radiolabelled somatostatin analogues to selectively target somatostatin receptor expressing (SSTR+) tumour cells. Use may stabilise disease and induce objective tumour response. ¹⁷⁷Lu-edotreotide is an innovative radiolabelled somatostatin analogue with promising efficacy and a favourable safety profile. Retrospective data in metastatic GEP-NETs treated with ≥2 cycles of ¹⁷⁷Lu-edotreotide demonstrate progression free survival (PFS) of ≥30 months. The active phase III COMPETE trial compares ¹⁷⁷Lu-edotreotide efficacy/safety vs everolimus in grade 1 and 2 GEP-NETs.

Trial design

COMPOSE is a prospective, randomized, controlled, open-label, multi-center phase III trial recruiting patients with well-differentiated aggressive grade 2 and 3 (Ki-67 index 15−55%), SSTR+, GEP-NETs. It will evaluate efficacy, safety and patient-reported outcomes of 1st- or 2nd-line treatment with ¹⁷⁷Lu-edotreotide PRRT compared to best standard of care [investigator´s choice of chemotherapy (CAPTEM or FOLFOX) or everolimus]. COMPOSE aims to randomize 202 patients 1:1 to a defined number of cycles of ¹⁷⁷Lu-edotreotide or the comparator. Primary endpoint is PFS, assessed every 12 weeks until disease progression (RECIST v1.1) or death, whichever occurs first. Secondary outcomes include overall survival, assessed up to 2 years after disease progression. Currently, 14 sites are already open for recruitment, including Australia, France, Spain, Sweden, the United Kingdom and the United States. More sites and countries will follow. Results are expected to increase treatment options for patients with well-differentiated aggressive grade 2 and 3 GEP-NETs, including for 1st-line therapy.

Clinical trial identification

NCT04919226.

Editorial acknowledgement

Editorial assistance was provided by Dr Eleanor Roberts, Insight Medical Writing.

Legal entity responsible for the study

ITM Solucin GmbH.

Funding

ITM Solucin GmbH.

Disclosure

C. Sierras, P. Harris: Financial Interests, Institutional, Full or part-time Employment: ITM. All other authors have declared no conflicts of interest.