The advancement of radiopharmaceutical therapies presents a potential shift in the treatment paradigm in personalized oncology.
ITM Isotope Technologies Munich SE, a leading radiopharmaceutical biotech company, is advancing its late-stage candidate, non-carrier-added (n.c.a) ¹⁷⁷Lu-edotreotide (also known as ITM-11 or ¹⁷⁷Lu-edotreotide), for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Following positive topline data from the pivotal Phase 3 COMPETE trial (NCT03049189) in March 2025, the company announced additional data from that trial at the congresses of the European Society for Medical Oncology (ESMO) and the European Association of Nuclear Medicine (EANM) in October 2025, further highlighting the clinical potential of n.c.a. ¹⁷⁷Lu-edotreotide in GEP-NETs.
Targeted Radiopharmaceutical Agent for GEP-NETs
¹⁷⁷Lu-edotreotide is a radiolabeled somatostatin receptor (SSTR) ligand being investigated for the treatment of SSTR-positive tumors, including GEP-NETs. The targeted, radiotherapeutic agent links a somatostatin analog to the beta-emitting radioisotope n.c.a. lutetium-177 (177Lu or Lu-177), enabling precise delivery of ionizing radiation directly to SSTR-expressing tumor cells. Once administered, it binds selectively to SSTR-positive cancer cells, is internalized, and releases localized radiation that induces DNA strand breaks and tumor cell death. This targeted approach is designed to minimize radiation exposure to surrounding healthy tissue, offering a key advantage over traditional external radiotherapy.
Clinical Evaluation of n.c.a. ¹⁷⁷Lu-edotreotide in Grade 1 & Grade 2 GEP-NETs: COMPETE Trial Study Design and Results
The COMPETE trial is a pivotal, multicenter, prospective, open-label, randomized Phase 3 study that evaluated n.c.a. ¹⁷⁷Lu-edotreotide vs. everolimus (Afinitor®; Novartis), a standard of care treatment for well-differentiated GEP-NETs. The study enrolled a total of 309 patients with inoperable or metastatic, progressive, SSTR-positive, Grade 1 or 2 tumors (Ki-67 ≤ 20%) who were treatment-naïve or progressed under prior therapy.
Participants were randomized to receive either n.c.a. ¹⁷⁷Lu-edotreotide (n=207, four intravenous cycles of n.c.a. ¹⁷⁷Lu-edotreotide administered every 3 months with nephroprotective amino-acid infusion) or targeted molecular therapy everolimus (n=102, 10 mg administered orally daily, maximum duration of 30 months) until disease progression or any cause for discontinuation.
The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and quality-of-life outcomes.
Key findings
Topline results from the Phase 3 COMPETE trial were presented at the European Neuroendocrine Tumor Society (ENETS) 2025 Conference, with additional efficacy, safety and subgroup analyses shared at ESMO on October 18, 2025. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in median PFS (mPFS) for patients treated with n.c.a. ¹⁷⁷Lu-edotreotide compared with everolimus.
- Significantly longer progression-free survival (PFS):
Patients receiving n.c.a. ¹⁷⁷Lu-edotreotide achieved a mPFS of 23.9 months, compared to 14.1 months with everolimus, based on central assessment.
- Higher objective response rates (ORR):
The trial also met its key secondary endpoint of ORR. N.c.a. ¹⁷⁷Lu-edotreotide demonstrated a central ORR of 21.9% and a local ORR of 30.5%, compared with 4.2% and 8.4%, respectively, for everolimus. These findings reflect improved tumor response and disease control with n.c.a. ¹⁷⁷Lu-edotreotide.
- Interim median overall survival (OS):
OS is another key secondary endpoint of the trial. Interim median OS was numerically higher, but at this point in time, not conclusive for 177Lu-edotreotide vs. everolimus (63.4 vs 58.7 months); p value=0.206; HR 0.78, 95% CI [0.5, 1.1]. The trial continues to collect OS data. More mature OS data will become available in the future.
- Subgroup analysis:
The mPFS was confirmed by a sensitivity analysis (local mPFS: 24.1 vs. 17.6 months) and observed across the patient subgroups of tumor origin (GE-NET, P-NET), tumor grade (Grade 1 or Grade 2), and treatment line (1st or 2nd line).
- Treatment-emergent adverse events:
Frequency of patients who experienced treatment-emergent adverse events (TEAEs) leading to premature study discontinuation was lower in the 177Lu-edotreotide arm.
| 177Lu-edotreotide (n=207) vs. Everolimus (n=102) | P value, Hazard Ratio (HR)/Confidence Interval (CI) | |
| ORR Central assessment Local assessment | 21.9% vs. 4.2% 30.5% vs. 8.4% | p<0.0001 p<0.0001 |
| Median Progression-Free Survival by Patient Subgroup (Central Assessment) 1 | ||
| Primary Tumor Origin Gastroenteric NET Pancreatic NET | 23.9 vs. 12.0 months 24.5 vs. 14.7 months | p=0.090; HR 0.64, 95% CI [0.38, 1.08] p=0.114; HR 0.70, 95% CI [0.45, 1.09] |
| Tumor Grade2 Grade 1 Grade 2 | 30 vs. 23.7 months 21.7 vs. 9.2 months | p=0.753; HR 0.89, 95% CI [0.42, 1.87] p=0.003; HR 0.55, 95% CI [0.37, 0.82] |
| Prior Medical Therapy Treatment-naïve (1st line) Prior therapy (2nd line) | NR3 vs.18.1 months 23.9 vs. 14.1 months | p=0.249; HR 0.60, 95% CI [0.25, 1.45] p=0.039; HR 0.68, 95% CI [0.47, 0.98] |
| 1Unstratified statistics 2Tumor grade was determined locally, per protocol 3Not reached | ||
| Premature Study Discontinuations | ||
| Frequency of Trial Discontinuations Related to Treatment-Emergent Adverse Events (TEAEs) | 1.8% vs. 15.2% | |
Safety and Dosimetry Demonstrate n.c.a. ¹⁷⁷Lu-edotreotide is Well-Tolerated and Targets Tumors
As presented, n.c.a. ¹⁷⁷Lu-edotreotide was well tolerated. The dosimetry data discussed/shown at EANM 2025 provided insight into the radiation distribution and absorbed dose profiles associated with n.c.a. ¹⁷⁷Lu-edotreotide. Dosimetry analyses were conducted in all patients randomized to the ¹⁷⁷Lu-edotreotide arm of the COMPETE trial, measuring radiation exposure to tumors and organs using serial SPECT/CT imaging and blood sampling. Results demonstrated high tumor uptake and low exposure to healthy organs, with mean absorbed doses well below established safety thresholds. These results support a favorable tumor-to-organ dose ratio in light of the potential of n.c.a. ¹⁷⁷Lu-edotreotide’s targeted delivery mechanism.
Tumor Absorbed Dose (AD) is Significantly Higher Than AD to Normal Organs
| Target/Organ | Mean Cumulative Absorbed Dose (Gy) | Safety threshold (Gy) | |
| Tumor | 110.0 ± 90.8 | – | |
| Whole body | 0.8 ± 0.6 | – | |
| Kidneys | 12.5 ± 4.4 | 23 | |
| Red bone marrow | 0.7 ± 0.4 | 2 |
A lower proportion of patients treated with n.c.a. ¹⁷⁷Lu-edotreotide showed treatment-emergent adverse events (TEAEs) compared to everolimus (82.5% vs. 97% overall). Most AEs were Grade 1–2 and manageable with supportive care.
177Lu-edotreotide Adverse Events Profile in Dose-limiting Organs Compared to Everolimus
| 177Lu-edotreotide, n=217 | Everolimus, n=99 | |
| n/% ≥1 Adverse events | n/%≥1 Adverse events | |
| Renal and urinary disorders | 32/14.7 % | 21/21.2 % |
| Blood and lymphatic disorders | 87/40.1 % | 41/41.4 % |
Conclusion
The COMPETE data reinforce the favorable safety profile of n.c.a. ¹⁷⁷Lu-edotreotide and support its potential as a tumor-targeted therapeutic option that combines clinical efficacy with limited toxicity. The trial demonstrated significant improvements in PFS and ORR compared with everolimus, with consistent benefit across tumor subtypes and lines of treatment. These results highlight the potential of targeted RPT with n.c.a. ¹⁷⁷Lu-edotreotide to redefine therapeutic strategies in neuroendocrine oncology.
Next Steps and Broader Clinical Development
The COMPETE trial marks an important milestone in the advancement of RPT for GEP-NETs.
In this global Phase 3 comparison, n.c.a. ¹⁷⁷Lu-edotreotide achieved a statistically significant improvement in mPFS over everolimus, along with dosimetry data supporting selective tumor targeting and low exposure to healthy organs. The consistency of these outcomes across multiple analyses presented at major oncology meetings reflects the consolidation of this therapeutic modality.
ITM is on track to file a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ¹⁷⁷Lu-edotreotide in the treatment of GEP-NETs in 2025. At this late stage of clinical development, ¹⁷⁷Lu-edotreotide has the potential to further improve patient treatment options with the exciting modality of RPTs.
These findings were made possible through the dedication and collaboration of patients, investigators, and clinical teams. Their participation has generated meaningful clinical data that advances RPT as a potential component of mainstream oncology care and may help improve outcomes across the cancer treatment landscape.
__
Clinical trials
Efficacy and Safety of 177Lu-edotreotide PRRT in GEP-NET Patients (COMPETE) – ClinicalTrials.gov ID NCT03049189
Highlights of Prescribing Information
Everolimus (Afinitor®; Novartis)[Prescribing Information]
References
[1] Capdevila, et al. Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with grade 1 or grade 2 GEP-NETs: Phase 3 COMPETE trial. Oral presentation. ESMO Congress. October 18, 2025. Berlin, Germany
[2] Deshayes, et al. Dosimetry of [177Lu]Lu-edotreotide in patients with grade 1 or grade 2 gastro-enteropancreatic neuroendocrine tumours: Results from the COMPETE Phase 3 trial. Oral presentation. European Association of Nuclear Medicine (EANM) Congress. October 6, 2025. Barcelona, Spain.
Featured image licensed under the Unsplash+ License.
DOI
