177Lu-satoreotide tetraxetan (177Lu-IPN01072), a novel somatostatin receptor 2 (SSTR2) antagonist, showed promising efficacy in patients with progressive NETs associated with myelotoxicity at 7.4 GBq/cycle administered activity. This phase I/II study evaluates the safety and preliminary efficacy of this agent by adjusting treatment regimen to limit radiation dose to bone marrow and kidneys.
Eligibility included progressive grade 1/2 NETs. Phase I comprises parts A and B. Part A involved, subject to toxicity, planned administration of 3 cycles of 4.5 GBq of 177Lu-satoreotide tetraxetan with a peptide mass of 300 μg and enrolled 15 patients. After safety evaluation, part B proceeded with the radioactivity/peptide mass ratio per cycle being escalated up to 6.0 GBq/300 μg or 4.5 GBq/300-1300 μg; 20 patients were enrolled at the interim analysis (IA) cut-off date.
Previous treatments of the 35 enrolled patients included surgery (69%), chemotherapy (20%), radiotherapy (14%), and prior or concomitant somatostatin analogues (77%). At the IA cut-off date, 28 had completed treatment, and 7 were still receiving planned cycles. Of these 28 patients, 22 (78.6%) had received 3 cycles with median cumulative radioactivity of ∼13 GBq, and 6 (21.4%) discontinued treatment. Overall, grade 3/4 related haematological adverse events (AEs) were reported in 12 patients (34.3%) with lymphopenia/decrease in lymphocyte counts in 6 (17.1%), thrombocytopenia/decrease in platelets count in 5 (14.3%), neutropenia in 2 (5.7%) and anemia in 1 (2.9%). No grade 3/4 renal toxicities were reported. For the 20 patients with adequate follow-up, disease control rate (DCR) at 12 months was 90% (95% CI: 68.3% - 98.8%).
This IA suggests that 177Lu-satoreotide tetraxetan has an acceptable safety profile in patients with NET using a lower administered activity per cycle than in earlier studies with this agent or current protocols using SSTR2 agonists. Promising efficacy results encourage the pursuit of its development in this indication.
Clinical trial identification
EudraCT: 2015-002867-41; NCT02592707.
Partner 4 Health, France, provided medical writing support in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
C. Ansquer: Advisory/Consultancy: Advanced Accelerator Applications - France. N. Germann, S. McEwan: Full/Part-time employment: Ipsen. D. Wild: Advisory/Consultancy: Ipsen. R.J. Hicks: Advisory/Consultancy, Shareholder/Stockholder/Stock options, with proceeds donated to my institution: Telix Pharmaceuticals. All other authors have declared no conflicts of interest.