Abstract CT254: COMPETE Phase III Trial - Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide vs. Everolimus in Progressive GEP-NET

Background Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) make up 75% of all NETs and are often diagnosed at an advanced state with only limited treatment options. Current standard therapies include somatostatin (SST) analogues and targeted drugs such as mTOR inhibitor Everolimus. While these treatments may achieve disease stabilization for a limited time, they rarely induce objective tumor remission. PRRT has recently emerged as a promising option providing more durable responses and potentially higher objective response rates. It uses radiolabeled SST analogues which specifically target and destroy tumor cells, this way significantly sparing benign tissues. PRRT with radiolabeled SST receptor (SSTR)-ligands, such as 177Lu-DOTATATE in NETTER-1, has shown promising results in the subgroup of progressive midgut NET, with significantly improved median progression-free survival (mPFS). 177Lu-Edotreotide is an innovative radiolabeled SST analogue, with a favourable safety profile and promising efficacy. Retrospective data in metastasized GEP-NET demonstrated a mPFS of 34.5 months. A prospective study of PRRT with an approved comparator has not yet been performed. Here we report the trial design and study objectives comparing the efficacy and safety of 177Lu-Edotreotide with Everolimus. Methods Trial design COMPETE (NCT03049189) is a prospective, randomized, controlled, open-label, multi-center Phase III study to evaluate the efficacy and safety of 177Lu-Edotreotide PRRT compared to Everolimus in patients with inoperable, progressive, SSTR+ GEP-NET. 300 patients with progressive Grade 1 and 2 GEP-NET will be randomized: 200 will receive a maximum of 4 cycles of 177Lu-Edotreotide (7.5 GBq/cycle) every 3 months or until diagnosis of progression; 100 will receive 10 mg Everolimus daily for 24 months, or until diagnosis of progression. Study treatment duration/patient is 24 months. Study Objectives Primary objective is to demonstrate prolonged mPFS in patients in the 177Lu-Edotreotide arm, vs. Everolimus. Secondary objectives include safety, objective response rates and overall survival after treatment with 177Lu-Edotreotide, vs. Everolimus. Conclusion COMPETE is the first pivotal study to compare PRRT in patients with Grade 1 and 2 GEP-NET using a comparator with an approved therapeutic. It is expected that COMPETE will increase their treatment options, including 1st-line therapy. Further studies with 177Lu-Edotreotide in NET patients with high unmet medical need are under review. Citation Format: Mona M. Wahba, Jonathan Strosberg, Anca Avram, Carina Mari Aparici. COMPETE Phase III Trial - Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-Edotreotide vs. Everolimus in Progressive GEP-NET [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT254.