FDA Accepts NDA for 177Lu-edotreotide in GEP-NETs

The FDA has accepted the new drug application (NDA) of the synthetic, targeted radiotherapeutic agent ¹⁷⁷Lu-edotreotide (ITM-11) for treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).¹ A Prescription Drug User Fee Act target date of August 28, 2026, has been set.

The acceptance follows recent pivotal developments in the phase 3 COMPETE trial (NCT03049189). Data from the final trial analysis were presented by Jaume Capdevila, MD, PhD, Vall d’Hebron University Hospital, at both the 2025 North American Neuroendocrine Tumor Society Multidisciplinary NET Medical Symposium and 2025 European Society for Medical Oncology Congress.

Here, Capdevila revealed that the trial met its primary end point of progression-free survival (PFS), with patients receiving ¹⁷⁷Lu-edotreotide exhibiting a significantly longer median PFS than those receiving the targeted molecular therapy everolimus (Afinitor) (23.9 vs 14.1 months; HR, 0.67; 95% CI, 0.48-0.95; P =.022).

The trial was also successful in meeting one of its key secondary end points, overall response rate (ORR), exhibiting ORRs of 21.9% with ¹⁷⁷Lu-edotreotide vs 4.2% with everolimus (P <.0001). Regarding the trial’s other secondary end point of overall survival (OS), the data appeared to favor patients treated with ¹⁷⁷Lu-edotreotide over those treated with everolimus.

In terms of safety, 82% of the patients in the investigational arm and 97% of patients in the control arm experienced adverse events (AEs); AEs led to study discontinuation in 1.8% of the investigational arm vs 15.2% of the control arm, respectively. Commonly reported AEs included nausea (30% vs 10.1%), diarrhea (14.3% vs 35.4%), asthenia (25.3% vs 31.3%), and fatigue (15.7% vs 15.2%), which were expected given the known safety profile of ¹⁷⁷Lu-edotreotide.

The NDA submission was supported by these statistically significant and clinically meaningful benefits.

“The FDA’s acceptance of our NDA is an important regulatory milestone in advancing this new radiopharmaceutical treatment option for patients with GEP-NETs,” said Celine Wilke, MD, chief medical officer of ITM, in a news release.¹ “In the [p]hase 3 COMPETE trial, ¹⁷⁷Lu-edotreotide demonstrated extended PFS, a straightforward dosing regimen, and a favorable safety profile, supporting its potential to improve the current treatment paradigm. We look forward to working closely with the FDA toward potential approval.”

About the COMPETE Trial

The phase 3 COMPETE trial is a randomized, open-label, multicenter study evaluating the efficacy and safety of ¹⁷⁷Lu-edotreotide compared with everolimus. The study’s primary end point is PFS; key secondary end points include OS and ORR.

Across 52 global sites, the trial enrolled a total of 309 patients with inoperable, progressive, somatostatin receptor–positive, grade 1 or grade 2 GEP-NETs who were randomly assigned 2:1 to receive either peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-edotreotide or everolimus.

Patients assigned to receive PRRT (n = 207) received 3 intravenous infusions of ¹⁷⁷Lu-edotreotide for a maximum of 4 cycles, while the comparator arm (n = 102) received a daily 10-mg dose of oral everolimus until progression or study completion.

REFERENCES

1. ITM announces FDA acceptance of new drug application (NDA) and PDUFA date for n.c.a. 177Lu-edotreotide (ITM-11) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. ITM Isotope Technologies Munich SE. November 13, 2025. Accessed November 13, 2025. https://tinyurl.com/bdha4yfx

2. Efficacy and safety of 177Lu-edotreotide PRRT in GEP-NET patients (COMPETE). ClinicalTrials.gov. Updated May 30, 2025. Accessed November 13, 2025. https://clinicaltrials.gov/study/NCT03049189