Further development of 177Lu-satoreotide tetraxetan is expected after promising data from a phase 1/2 trial were recently published.
The use of 177Lu-satoreotide tetraxetan (177Lu-OPS201; satoreotide), a radiolabeled somatostatin receptor (SSTR) antagonist, induces activity in patients with SSTR2-positive neuroendocrine tumors (NETs), according to published phase 1/2 study results (NCT02592707).1,2
Results come from 38 patients with SSTR2-positive NETs treated with 177Lu-satoreotide tetraxetan at study sites in North America and Europe. A partial response in the form of reduction in tumor size was observed in 21.1% of patients for an objective response rate of 21.1% (95% CI, 9.6%-36.3%) and a disease control rate of 94.7%. The median duration of response to 177Lu-satoreotide tetraxetan was 17.9 months (95% CI, 6.8 to not estimable [NE]).1
The investigator-assessed median progression-free survival among patients treated with 177Lu-satoreotide tetraxetan was 28.1 months (95% CI, 19.4 months-NE).
Patients in the study were exposed to treatment for a median of 127 days (range 1-274), and all of them experienced at least 1 treatment-emergent adverse event (TEAE). Treatment-related events occurred in 97.5%, and grade 3 or higher TEAEs were observed in 42.5% of patients. No TEAEs led to death during the study. Treatment reductions were required for 5.0% of patients, and treatment interruptions occurred in 12.5% as a result of TEAEs. Treatment delays due to TEAEs occurred in 5.0% of patients. In terms of dose-limiting toxicities, only 9 were observed in 6 patients.
The exploration of 177Lu-satoreotide tetraxetan in the phase 1/2 study comes after positive preclinical models showing that the SSTR antagonists have more stable tumor uptake in addition to higher tumor uptake compared with cytotoxic therapy.3 Moreover, the research follows a phase 1 study of 177Lu-satoreotide tetraxetan in which the agents demonstrated encouraging clinical activity in patients with heavily-treated NETs, which can be difficult to treat, according to experts.4
“Almost no NET case is alike. It can arise in many different organs, and the spectrum of aggressiveness is from the slowest growing solid tumors to the fastest growing. Also, the treatment can be complex depending on whether it's liver dominant or not, the differentiation grade, stage, and somatostatin receptor expression, Jonathan Strosberg, MD, previously told Targeted Oncology™, in an interview.
Patients in the phase 1/2 received 177Lu-satoreotide tetraxetan 13.0 GBq for 4 to 5 8-week cycles. Patients were screened for 4 weeks to begin, then treated. Patients also had the option to have up to 2 additional cycles of treatment (16 weeks). Patients on the study continued to be followed for long-term safety for 5 years.
Overall, the 177Lu-satoreotide tetraxetan was found to be a well-tolerated therapy with promising efficacy, warranting further development of the drug for the treatment of patients with advanced and/or progressive NETs.
“These exciting new data demonstrate the great potential of our targeted radiopharmaceutical, satoreotide, for treating patients with advanced neuroendocrine tumors. Not only did a high proportion of treated patients achieve stable disease or better, but they did so on a lower dose of radiation than the investigators initially thought was needed. These results will greatly assist Ariceum in further developing satoreotide for hard-to-treat neuroendocrine cancers such as small cell lung cancer," said Manfred Rüdiger, PhD, chief executive officer, Ariceum Therapeutics, in a press release.
1. Wild D, Grønbæk H, Navalkissoor, S, et al. A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours. Eur J Nucl Med Mol Imaging. Published September 18, 2023. doi: 10.1007/s00259-023-06383-1.
2. Ariceum Therapeutics' targeted radiopharmaceutical 177Lu-satoreotide exhibits promising clinical response and good tolerability profile in patients with advanced neuroendocrine tumours. News release. Ariceum Therapeutics. September 28, 2023. Accessed October 3, 2023.
3. Dalm SU, Nonnekens J, Doeswijk GN, et al. Comparison of the therapeutic response to treatment with a 177Lu-labeled somatostatin receptor agonist and antagonist in preclinical models. J Nucl Med. 2016;57:260–5. doi: 10.2967/jnumed.115.167007
4. Reidy-Lagunes D, Pandit-Taskar N, O’Donoghue JA, et al. Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist 177Lu-satoreotide tetraxetan. Clin Can Res. 2019;25(23):6939-6947. doi: 10.1158/1078-0432.CCR-19-1026