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

Abstract

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 [¹⁷⁷Lu]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 [¹⁷⁷Lu]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 [¹⁷⁷Lu]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 [¹⁷⁷Lu]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: [¹⁷⁷Lu]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.

Keywords: Clinical trial; Neuroendocrine tumours; Peptide receptor radionuclide therapy; Somatostatin receptor antagonist; [177Lu]Lu-satoreotide tetraxetan.

Fig. 1

Administered activity and peptide amounts of [¹⁷⁷Lu]Lu-satoreotide tetraxetan in cycles 1 to 3 of part A and part B of the study. Note that four patients in cohort 3 and two patients in cohort 6 received additional treatment cycles (see Table 2). The study had a SRC (part A) and a DRB (part B). During part B, each escalation cohort (whether of administered activity or peptide amount) was evaluated by the DRB. DRB Data Review Board, SRC Safety Review Committee

Fig. 2

Overview of study procedures during part A and part B of the study. EOCT end-of-core-trial, W weeks, Y years

Fig. 3

Patient disposition

Fig. 4

Kaplan-Meier plot for PFS based on A independent central review and B investigator assessment (RECIST version 1.1; per-protocol population). Central review was performed up until the end of treatment cycles, ending at 7 months for part A and 11 months for part B. When neither tumour progression nor death occurred, the date of the last central assessment was taken. PFS progression free survival, RECIST Response Evaluation Criteria in Solid Tumours