177Lu-Edoterotide Handed CRL by FDA For GEP-NETs Treatment

The FDA has issued a complete response letter (CRL) to ¹⁷⁷Lu-edoterotide (ITM-11) for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), according to a news release from the developer, ITM Isotope Technologies Munich SE (ITM).¹

In the letter, the agency stated that it was unable to approve the new drug application (NDA) in its present form, citing chemistry, manufacturing, and controls (CMC)- and third-party commercial facility-related concerns requiring remediation to permit the application’s approval. The FDA did not identify any clinical or nonclinical concerns regarding the efficacy or safety profile of ¹⁷⁷Lu-edoterotide, and the developers are reviewing the decision to determine next steps. Moreover, the developers intend to resubmit the NDA for FDA review.

“Our confidence in [¹⁷⁷Lu-edoterotide’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,” Andrew Cavey, MD, chief executive officer of ITM, stated in the release.¹ “Our pivotal [phase 3] COMPETE trial [NCT03049189] data package stands, and our goal remains unchanged as we work toward bringing [¹⁷⁷Lu-edoterotide] to patients living with advanced GEP-NETs.”

Efficacy data for the COMPETE trial presented at the 22nd Annual Neuroendocrine Tumor Society (ENETS) 2025 Conference and exhibited in a news release by the developers showed a median progression-free survival (PFS) of 23.9 months with ¹⁷⁷Lu-edotreotide compared with 14.1 months with everolimus (Afinitor; HR, 0.67; 95% CI, 0.48-0.95; P = .022), the latter of which is a standard-of-care therapy for patients with GEP-NETs.²

Additionally, as of the January 2025 data cutoff, the interim median overall survival (OS) was 63.4 months vs 58.7 months, respectively, with the investigational radiopharmaceutical demonstrating numerically higher values that were not conclusive for significance (HR 0.78; 95% CI, 0.5-1.1; P = .206).

Moreover, response findings from the European Society for Medical Oncology (ESMO) 2025 Congress and presented in a news release by the developers showed an objective response rate of 21.9% with ¹⁷⁷Lu-edotreotide vs 4.2% with everolimus (P <.0001) per central assessment.³ Per local assessment, the ORR was 30.5% vs 8.4%, respectively (P <.0001).

Previous health-related quality of life (HRQOL) outcomes from the COMPETE trial, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that ¹⁷⁷Lu-edotreotide conferred better health-related quality of life (HRQOL) outcomes vs everolimus.⁴ The global health status and QOL scores were stable with ¹⁷⁷Lu-edotreotide, with a least-squares mean change from baseline of 0.9 (95% CI, –2.7 to 4.4), and decreased with everolimus, with a value of –9.9 (95% CI, –13.9 to –6.0).

A total of 309 patients with inoperable, progressive, grade 1 or grade 2 somatostatin receptor (SSTR)-positive NETs of gastroenteric or pancreatic origin were enrolled. Patients were randomly assigned 2:1 to receive up to 4 cycles of 7.5 GBq of ¹⁷⁷Lu-edotreotide with a nephroprotective amino acid solution every 3 months (n = 207), or 10 mg of oral everolimus daily for up to 30 months (n = 102).

The primary end point of the trial was PFS. Secondary end points included ORR and OS.

Regarding safety, treatment-emergent adverse effects (TEAEs) related to each agent occurred in 82.5% of patients who received ¹⁷⁷Lu-edotreotide compared with 97.0% of patients who received everolimus. One grade 2 serious TEAE of myelodysplastic syndrome was reported, and no unexpected TEAEs were observed. The developers noted that the agent appeared to be well tolerated.

The FDA previously accepted a new drug application for ¹⁷⁷Lu-edotreotide as a treatment for patients with GEP-NETs in November 2025, with a Prescription Drug User Fee Act goal date of August 28, 2026.⁵

References

1. ITM Receives Complete Response Letter for 177Lu-edotreotide (ITM-11). News release. ITM Isotope Technologies Munich SE. August 10, 2026. Accessed August 10, 2026. https://tinyurl.com/38ycb62j
2. ITM presents positive topline phase 3 COMPETE trial data with n.c.a. 177Lu-edotreotide (ITM-11), a targeted radiopharmaceutical therapy, in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors at the ENETS 2025 conference. News release. ITM Isotope Technologies Munich SE. March 6, 2025. Accessed August 10, 2026. https://tinyurl.com/37a6k7kb
3. 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. ITM Isotope Technologies Munich SE. October 18, 2025. Accessed August 10, 2026. https://tinyurl.com/3jm7kr5w
4. Capdevila J, Jann H, Verberne HJ, et al. Quality of life in patients with gastroenteropancreatic neuroendocrine tumors receiving 177Lu-edotreotide or everolimus: results from the COMPETE study. J Clin Oncol. 2026;44(suppl 16):4171. doi:10.1200/JCO.2026.44.16_suppl.4171
5. 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 August 10, 2026. https://tinyurl.com/2zvjxy6s