A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours

• Published in: European journal of nuclear medicine and molecular imaging 2023-12, Vol.51 (1), p.183-195
• Main Authors: Wild, Damian, Grønbæk, Henning, Navalkissoor, Shaunak, Haug, Alexander, Nicolas, Guillaume P., Pais, Ben, Ansquer, Catherine, Beauregard, Jean-Mathieu, McEwan, Alexander, Lassmann, Michael, Pennestri, Daniele, Volteau, Magali, Lenzo, Nat P., Hicks, Rodney J.
• Format: Article
• Language: English
• Subjects: Bone marrow; Cardiology; Disease control; Dosimetry; Effectiveness; Follow-Up Studies; Health services; Humans; Imaging; Lutetium isotopes; Lymphopenia; Medicine; Medicine & Public Health; Neoplasms; Neuroendocrine tumors; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - radiotherapy; Neutropenia; Nuclear Medicine; Octreotide - adverse effects; Oncology; Organometallic Compounds - adverse effects; Original; Original Article; Orthopedics; Patients; Peptides; Radiation dosage; Radiology; Receptors; Receptors, Somatostatin; Safety; Somatostatin; Somatostatin receptors; Thrombocytopenia; Tumors
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-023-06383-1

Purpose We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [ 177 Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. Methods This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [ 177 Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [ 177 Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 μg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. Results Median cumulative administered activity of [ 177 Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment‑related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3–99.4), and overall response rate was 21.1% (95% CI: 9.6–37.3). Conclusion [ 177 Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. Trial registration ClinicalTrials.gov, NCT02592707. Registered October 30, 2015.