COMPETE Trial Data Shows 177Lu-edotreotide Improves Progression-Free Survival in SSTR-GEP-NETs

ITM Isotope Technologies Munich SE announced positive topline data from its Phase 3 COMPETE trial in patients with Grade 1 or Grade 2 somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The trial results demonstrated that n.c.a. ¹⁷⁷Lu-edotreotide (also known as ITM-11 or ¹⁷⁷Lu-edotreotide), a proprietary, synthetic, targeted radiotherapeutic agent, met the primary endpoint and significantly prolonged progression-free survival in patients when compared to everolimus, a standard of care cancer treatment. The data were presented by study investigator Jaume Capdevila, MD, PhD, at the 22nd Annual European Neuroendocrine Tumor Society (ENETS) 2025 Conference.

“COMPETE is the first pivotal trial comparing a radiopharmaceutical drug candidate to a targeted molecular therapy without the routine use of accompanying somatostatin analogues in this GEP-NET patient population. These data show unequivocal support for ¹⁷⁷Lu-edotreotide's potential benefit in extending PFS,” said Dr Capdevila, senior medical oncologist at Vall d'Hebron University Hospital, Barcelona. “Additionally, ¹⁷⁷Lu-edotreotide's convenient dosing schedule and favorable safety results reinforce its potential as a compelling new treatment option.”

COMPETE is a prospective, randomized, controlled, open-label Phase 3 trial that enrolled 309 patients with inoperable, progressive, Grade 1 or Grade 2 somatostatin receptor-positive neuroendocrine tumors of gastroenteric or pancreatic origin (Ki-67 ≤20%) in Europe, the United States, Australia and South Africa. The study objectives were to evaluate the efficacy and safety of ¹⁷⁷Lu-edotreotide compared to everolimus. ¹⁷⁷Lu-edotreotide is comprised of non-carrier-added (n.c.a.) lutetium-177, a therapeutic β-emitting radioisotope, and edotreotide, a somatostatin receptor agonist. It is the first radiopharmaceutical to be tested in the GEP-NET patient population using non-carrier-added lutetium, which has a higher isotopic purity than carrier-added lutetium.

Patients were randomized 2:1 to receive 7.5 GBq of ¹⁷⁷Lu-edotreotide with a nephroprotective amino acid solution every three months for up to four cycles, or everolimus 10 mg daily for up to 30 months, or until disease progression. There were 207 patients on the ¹⁷⁷Lu-edotreotide arm and 102 on the everolimus arm. Dosimetry was used to assess the absorbed dose in tumors compared to that in healthy tissue to enhance safety and efficacy monitoring of the study drug in patients.

“The COMPETE results represent a major step forward in the development of new treatment options for people living with progressive, inoperable GEP-NETs. By extending progression-free survival by almost ten months compared to standard of care in this trial, ¹⁷⁷Lu-edotreotide showed the potential to significantly improve the treatment paradigm for physicians and their patients,” said Jonathan Strosberg, MD, past president, North American Neuroendocrine Tumor Society and chair, GI Research Program, Moffitt Cancer Center and Research Institute in Tampa, FL.

The median overall survival as of January 21, 2025 was 63.4 months for the ¹⁷⁷Lu-edotreotide arm and 58.7 months for the everolimus arm. While not statistically significant, the interim analysis showed a favorable trend for ¹⁷⁷Lu-edotreotide. Patients were permitted to start an alternative therapy after disease progression, potentially confounding the overall survival data. Overall survival data will continue to be updated.

¹⁷⁷Lu-edotreotide was observed to be well-tolerated and there were no unforeseen treatment-emergent adverse events. Additional data, including objective response rate, subgroup analyses, quality of life assessments and dosimetry, are currently being evaluated and expected to be submitted for presentations at future medical meetings. ITM is planning to submit a New Drug Application (NDA) to the FDA in 2025.

“These successful results validate our decision to design a pivotal Phase 3 trial directly comparing a targeted radiopharmaceutical against a targeted molecular therapy in Grade 1/2 GEP-NETS, underscoring our commitment to improving the lives of people living with this challenging cancer,” said Andrew Cavey, MD, PhD, chief executive officer, ITM. “With this successful readout, ¹⁷⁷Lu-edotreotide becomes the first drug candidate in ITM’s broad portfolio of early- to late-stage radiopharmaceuticals to deliver positive Phase 3 results and progress towards NDA submission and commercial launch preparations. Together, with our global isotopes manufacturing business, robust supply chain, and experienced clinical and commercial team, we believe we are uniquely positioned as a standout leader in the fast-growing radiopharmaceutical industry.”