COMPETE Trial: ITM-11 Tops Everolimus for GEP-NET PFS and OS

Final analysis from the phase 3 COMPETE trial (NCT03049189) demonstrated that ITM-11 (¹⁷⁷Lu-edotretide) met its primary and secondary end points in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) compared with everolimus. Data were presented by Jaume Capdevila, MD, PhD, of Vall d'Hebron University Hospital, at the 2025 European Society for Medical Oncology (ESMO) Congress on October 18, and at the North American Neuroendocrine Tumor Society 2025 Symposium on October 25.¹

The primary end point was progression-free survival (PFS), which was reached with statistically significant and clinically meaningful improvement. The median PFS was significantly longer in patients who received ITM-11 compared with those who received everolimus. The secondary end point of the trial was overall survival, which was also identified to be higher in patients who received ITM-11 vs everolimus.²

There was a total of 207 patients in the ITM-11 group and 102 patients in the everolimus group. The median ages of both groups were 65 (ITM-11) and 61 (everolimus). The majority of patients in both groups were male, had grade 2, nonfunctional GEP-NETs, and had received prior therapy.

COMPETE Trial Findings

COMPETE met its primary end point of PFS, which proved to be significantly longer in patients treated with ITM-11 vs everolimus. The central assessment was 23.9 vs 14.1 months, respectively (HR, 0.67; 95% CI, 0.48-0.95; P =.022). The local assessment was 24.1 vs 17.6 months (HR, 0.66; 95% CI, 0.48-0.91; P =.010).

In the subgroup analysis of PFS by tumor origin, modified (m)PFS was numerically longer in GE-NETs and P-NETs in the ITM-11 arm. In GE-NETs, the mPFS was 23.9 vs 12 months for everolimus (HR 0.64; 95% CI, 0.38-1.08; P =.090). In P-NETs, the mPFS was 24.5 vs 14.7 months (HR, 0.70; 95% CI, 0.45–1.09; P =.114).

It was also identified that mPFS was numerically longer in grade 1 and significantly longer in grade 2 tumors in the ITM-11 arm. Grade 1 was 30 vs 23.7 months (HR, 0.89; 95% CI, 0.42-1.8; P =.753), and grade 2 was 21.7 vs 9.2 months (HR 0.55; 95% CI, 0.37-0.82; P =.0003).

In exploring PFS by prior therapy, it was identified that mPFS was numerically longer in the first line and significantly longer in the second line in the ITM-11 arm. First-line data showed the mPFS was not reached in the ITM-11 vs 18.1 months (HR, 0.60; 95% CI, 0.25-1.45; P =.249), and second-line data showed 23.9 vs 14.1 months (HR, 0.68; 95% CI, 0.47-0,98; P=.039).

Overall response rates, one of the secondary end points of the trial, were found to be significantly higher in the ITM-11 arm. Central assessment was 21.9% vs 4.2% (P <.0001), and local assessment was 30.5% vs 8.4% (P <.0001).

Safety Profile

Adverse events (AEs) related to the drug study were experienced by 82% of patients in the ITM-11 group and 97% of patients in the everolimus group. The most common AEs reported were nausea (30% vs 10.1%, respectively), diarrhea (14.3% vs 35.4%), asthenia (25.3% vs 31.3%), and fatigue (15.7% vs 15.2%). These AEs were expected based on the known safety profile of ITM-11.²

AEs leading to premature study discontinuation occurred in 1.8% of the ITM-11 group vs 15.2% of the everolimus group. Dose modification or discontinuation rates were 3.7% vs 52.5%, respectively, and the percentage of patients with delayed study drug administration due to toxicity was 0.9% and 0%.²

Dosimetry data showed targeted tumor uptake with low exposure to healthy organs, with normal organ-absorbed doses well below safety thresholds.

Patient Characteristics

Patient inclusion criteria included being 18 years or older; having well-differentiated, nonfunctional GE-NET or functional/nonfunctional P-NET; having grade 1/2 unresectable or metastatic, progressive, SSRT-positive disease; and being treatment-naive to first-line therapies or progressing under prior second-line therapies.^1,2

Morphologic imaging was conducted in 3-month intervals. The PFS follow-up was done every 3 months after the first 30 days. Long-term follow-up was done every 6 months.

“With these data combining extensive dosimetry information from more than 200 patients included in a prospective trial, ITM is laying the groundwork for improved therapeutic decision-making by providing important insights into tumor uptake and treatment variability,” Emmanuel Deshayes, MD, PhD, professor in biophysics and nuclear medicine at the Montpellier Cancer Institute in France, said in a news release.² “It may offer clinically meaningful implications for optimizing individualized patient management.”

Dosimetry data from COMPETE shaped the design of ITM’s phase 3 COMPOSE (NCT04919226)⁴ trial with ITM-11 in well-differentiated, aggressive grade 2 or grade 3 SSTR-positive GEP-NET tumors, as well as the upcoming phase 1 pediatric KinLET (NCT06441331) study in SSTR-positive tumors.

DISCLOSURES: Capdevila noted grants and/or research support from Advanced Accelerator Applications, AstraZeneca, Amgen Inc, Bayer, Eisai Co, Gilead Sciences Inc, ITM, Novartis, Pfizer Inc, and Roche; participation as a speaker, consultant, or adviser for Advanced Acclerator Applications, Advanz Pharma, Amgen Inc, Bayer, Eisai Co, Esteve, Exelixis Inc, Hutchmed, Ipsen Pharma, ITM, Lilly, Merck Serono, Novartis, Pfizer Inc, Roche, and Sanofi; position as advisory board member for Amgen Inc, Bayer, Eisai Co, Esteve, Exelixis Inc, Ipsen Pharma, ITM, Lilly, Novartis, and Roche; and a leadership role and chair position for the Spanish Task Force for Neuroendocrine and Endocrine Tumours Group (GETNE).

REFERENCES

1. ITM announces analyses from phase 3 COMPETE data showing higher objective response rates with n.c.a. 177Lu-edotreotide (ITM-11) vs. everolimus across subgroups of patients with GEP-NETs at NANETS 2025 Annual Symposium. News release. ITM. October 25, 2025. Accessed October 27, 2025. https://tinyurl.com/yfme9pwr

2. ITM presents dosimetry data from phase 3 COMPETE trial supporting favorable efficacy and safety profile with n.c.a. 177Lu-edotreotide (ITM-11) in patients with gastroenteropancreatic neuroendocrine tumors at EANM 2025 Annual Congress. News release. ITM. October 8, 2025. Accessed October 18, 2025. https://tinyurl.com/3nuscs4m

3. Lutetium 177Lu-edotreotide versus best standard of care in well-differentiated aggressive grade-2 and grade-3 gastroenteropancreatic neuroendocrine tumors (GEP-NETs) – COMPOSE (COMPOSE). ClinicalTrials.gov. Updated September 10, 2025. Accessed October 18, 2025. https://www.clinicaltrials.gov/study/NCT04919226

4. Phase I trial to determine the dose and evaluate the PK and safety of lutetium Lu 177 edotreotide therapy in pediatric participants with SSTR-positive tumors (KinLET). ClinicalTrials.gov. Updated September 19, 2025. Accessed October 18, 2025. https://www.clinicaltrials.gov/study/NCT06441331