Phase I Trial of Well-Differentiated Neuroendocrine Tumors (NETs) with Radiolabeled Somatostatin Antagonist 177Lu-Satoreotide Tetraxetan

Clin Cancer Res. 2019 Dec 1;25(23):6939-6947. doi: 10.1158/1078-0432.CCR-19-1026. Epub 2019 Aug 22.


Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist 177Lu-satoreotide tetraxetan.

Patients and methods: Twenty patients with advanced SSTR2-positive NETs were treated with 177Lu-satoreotide tetraxetan. Patients first underwent a dosimetry study with 177Lu-satoreotide tetraxetan to determine the therapeutic activity that could be safely administered. This activity was split into two equal cycles to be delivered 3 months apart. The maximum activity was 7.4 GBq per cycle.

Results: Of 20 patients with NETs (one lung, seven small bowel, nine pancreatic, one gastric, one rectal, one kidney; mean prior treatments: three), six received one cycle of 177Lu- satoreotide tetraxetan and 14 received two cycles. Hematologic toxicity after cycle 1 was mild-moderate and reversed before cycle 2. However, grade 4 hematologic toxicity occurred in four of seven (57%) patients after cycle 2 of 177Lu-satoreotide tetraxetan. The study was suspended, and the protocol modified to limit the cumulative absorbed bone marrow dose to 1 Gy and to reduce prescribed activity for cycle 2 by 50%. The best overall response rate was 45% [5% complete response (1/20), 40% partial response (8/20)]; with 40% stable disease (8/20) and 15% progression of disease (3/20). Median progression-free survival (PFS) was 21.0 months (95% CI, 13.6-NR).

Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 177Lu-satoreotide tetraxetan. Additional studies are ongoing to determine optimal therapeutic dose/schedule.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Chelating Agents / chemistry
  • Female
  • Follow-Up Studies
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Humans
  • Lutetium / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / analogs & derivatives*
  • Octreotide / therapeutic use
  • Prognosis
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / therapeutic use*
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Young Adult


  • Chelating Agents
  • Heterocyclic Compounds, 1-Ring
  • Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Lutetium
  • Lutetium-177
  • Octreotide