FDA Does Not Approve 177Lu-Edotreotide for GEP-NETs

The FDA issued a complete response letter (CRL) to a new drug application (NDA) for ¹⁷⁷Lu-edotreotide (ITM-11) for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to a news release from ITM, the developer of the radioligand therapy.¹

The CRL did not cite any clinical issues regarding the NDA. It explained the reason for its rejection of the application as being related to outstanding chemistry, manufacturing, and controls (CMC) items and findings tied to an inspection of a third-party commercial manufacturing facility.

The primary clinical support for the NDA came from the phase 3 COMPETE trial (NCT03049189) comparing ¹⁷⁷Lu-edotreotide with everolimus (Afinitor).² Patients treated with the radioligand therapy had a median progression-free survival (PFS) of 23.9 months, compared with 14.1 months with everolimus (HR, 0.67; 95% CI, 0.48-0.95; P = .022).

An interim analysis of overall survival (OS) also numerically favored ¹⁷⁷Lu-edotreotide, with a median of 63.4 months versus 58.7 months for everolimus, although that difference had not reached statistical significance at the time of analysis (HR, 0.78; 95% CI, 0.5-1.1; P = .206).² The trial additionally met a key secondary end point, with an objective response rate of 21.9% in with ¹⁷⁷Lu-edotreotide compared with 4.2% with everolimus.³

“Our confidence in ITM-11's therapeutic potential has not wavered, and we are committed to working closely with the FDA and our partners to address the items outlined in the CRL. Our pivotal COMPETE trial data package stands, and our goal remains unchanged as we work toward bringing ITM-11 to patients living with advanced GEP-NETs,” Andrew Cavey, chief executive officer of ITM, stated in a news release.

Safety Profile of ¹⁷⁷Lu-Ddotreotide

Any-grade treatment-related adverse events (AEs) in the COMPETE trial were reported in 82% of patients treated with ¹⁷⁷Lu-edotreotide, compared with 97% of those treated with everolimus.³ Grade 3 or 4 treatment-related AEs occurred less often with the radioligand therapy, affecting 18% of patients versus 40% of those on everolimus.

The most frequently reported treatment-related AEs with ¹⁷⁷Lu-edotreotide were diarrhea and nausea, each occurring in 36% of patients, along with asthenia in 33%. Among patients who received everolimus, the most common AEs were diarrhea (45%), asthenia (36%), and anemia (27%). AEs leading to premature treatment discontinuation were considerably less frequent with ¹⁷⁷Lu-edotreotide, occurring in 1.8% of patients compared with 15.2% of those who received everolimus.

COMPETE Trial Design and Patient Population

COMPETE enrolled 309 patients across 49 sites worldwide with inoperable, progressive, grade 1 or grade 2 GEP-NETs of gastroenteric or pancreatic origin who were positive for somatostatin receptor (SSTR) expression and had a Ki-67 proliferation index of 20% or lower.2 Eligible patients were either treatment naive or had experienced disease progression on one prior line of therapy.² Participants were randomly assigned in a 2:1 ratio to receive 7.5 GBq of ¹⁷⁷Lu-edotreotide plus a nephroprotective amino acid solution every 3 months for up to 4 cycles, or 10 mg of everolimus daily for up to 30 months or until disease progression.

Next Steps

¹⁷⁷Lu-edotreotide is also being evaluated in COMPOSE (NCT04919226), a phase 3 trial comparing the radioligand therapy with best standard of care (investigator's choice of chemotherapy or everolimus) in patients with well-differentiated, aggressive grade 2 or grade 3 SSTR-positive GEP-NETs.⁴

ITM reported in the news release that it remains confident in the strength of the 177Lu-edotreotide data package and intends to resubmit the NDA once the CMC and facility-related items outlined in the CRL have been addressed.¹ The company noted that it is coordinating with external manufacturing partners to determine next steps.

REFERENCES

1. ITM Isotope Technologies Munich SE. ITM receives complete response letter for 177Lu-edotreotide (ITM-11). News release. Published August 10, 2026. Accessed August 11, 2026. https://tinyurl.com/53j27rv4

2. Walter T, et al. [177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial. Lancet. Published online July 2, 2026. doi:10.1016/S0140-6736(26)00604-5

3. ITM Isotope Technologies Munich SE. ITM announces phase 3 COMPETE data demonstrating a statistically significant higher objective response rate with n.c.a. 177Lu-edotreotide (ITM-11) vs everolimus in patients with gastroenteropancreatic neuroendocrine tumors at ESMO 2025. News release. Published 2025. Accessed August 11, 2026. https://tinyurl.com/2t5vzhs8

4. ClinicalTrials.gov. Efficacy and safety of 177Lu-edotreotide versus best standard of care in GEP-NET patients (COMPOSE). NCT04919226. Updated 2026. Accessed August 11, 2026. https://clinicaltrials.gov/study/NCT04919226