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

Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of NETs. We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist 177Lu-satoreotide tetraxetan. EXPERIMENTAL DESIGN: 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 three months apart. The maximum activity was 7.4 GBq per cycle. Results: Of 20 NET patients (1 lung, 7 small bowel, 9 pancreatic, 1 gastric, 1 rectal, 1 kidney; mean prior treatments: 3), 6 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 4/7 (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 1Gy 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). Conclusion: In this trial of heavily treated NETs, preliminary data are promising for the use of 177Lu-satoreotide tetraxetan. Additional studies are on-going to determine optimal therapeutic dose/schedule.