A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen for ⁶⁸Ga-Satoreotide Trizoxetan as an Imaging Agent in Patients with Gastroenteropancreatic Neuroendocrine Tumors

Abstract

68 Ga-satoreotide trizoxetan is a novel somatostatin receptor antagonist associated with high sensitivity and reproducibility in neuroendocrine tumour (NET) detection and localisation.However, the optimal peptide mass and radioactivity ranges for 68 Ga-satoreotide trizoxetan have not yet been established. We therefore aimed to determine its optimal dosing regimen in patients with metastatic gastroenteropancreatic NETs in a prospective, randomised, 2×3 factorial, multicentre, phase II study.Methods: Patients received 68 Ga-satoreotide trizoxetan at a peptide mass of 5-20 µg on day 1 of the study and of 30-45 µg on day 16-22, at one of three gallium-68 radioactivity ranges . Whole-body PET/CT imaging was performed 50-70 minutes after each injection. The primary endpoint was the detection rate of NET lesions imaged by 68 Gasatoreotide trizoxetan relative to contrast-enhanced CT (CECT) (for each of the six peptide mass/radioactivity range combinations).Results: Twenty-four patients were evaluated in the per-protocol analysis. The median number of lesions detected by 68 Ga-satoreotide trizoxetan PET/CT or PET only was at least twice as high as the number of lesions detected by CECT across the six studied peptide mass dose/radioactivity range combinations. There were no differences between the two peptide mass ranges and between the three radioactivity ranges in the number of identified lesions. However, a trend towards a lower 3 relative lesion count was noted in the liver for the 40-80 MBq range. No relationship was observed between the radioactivity range per patient's body weight (MBq/kg) and the number of lesions detected by 68 Ga-satoreotide trizoxetan. Median diagnostic sensitivity of 68 Ga-satoreotide trizoxetan PET/CT, based on the number of lesions per patient, ranged from 85% to 87% across the different peptide mass and radioactivity ranges. Almost all reported adverse events were mild and self-limiting. Conclusion:A radioactivity of 100-200 MBq with a peptide mass up to 50 μg were confirmed as the optimal dosing regimen for 68 Ga-satoreotide trizoxetan to be used in future phase III studies.

A novel read methodology to evaluate the optimal dose of 68Ga-satoreotide trizoxetan as a PET imaging agent in patients with gastroenteropancreatic neuroendocrine tumours: a phase II clinical trial

“…In terms of radioactivity ranges, the IQSs for the 68 Gasatoreotide trizoxetan PET/CT and PET only scans were lower for the 40-80 MBq range, especially with the PET only images. These results, along with the other published data from the study [18], confirmed that this radioactivity range of 68 Ga-satoreotide trizoxetan cannot be recommended for phase III development, particularly given that it has never been evaluated in prior studies with other 68 Ga-labelled agents. The combination of 40-80 MBq and 5-20 µg appears to have the poorest quality of reads, as illustrated by the IQSs for 68 Gasatoreotide trizoxetan PET/CT and PET only scans when compared to other peptide mass and radioactivity range combinations, suggesting a potential peptide mass dose effect.…”

“…The primary results of this phase II study [18] showed that the ratio of the number of lesions detected by 68 Gasatoreotide trizoxetan imaging to the number of lesions detected by contrast-enhanced CT was overall consistent across different peptide mass and radioactivity range combinations (5-20 or 30-45 µg with one of three gallium-68 radioactivity ranges: 40-80, 100-140, or 160-200 MBq). However, a trend towards a lower ratio in the liver was noted for the radioactivity range of 40-80 MBq compared to higher radioactivity ranges.…”

“…: 2016-004928-39) was conducted between September 2017 and August 2019, using an open-label, reader-blinded, 2 × 3 factorial design. The methodology and primary results have been reported elsewhere [18]. In summary, a total of 24 adult patients with well-differentiated, metastatic, grade 1/2, SSTR-positive GEP-NETs were randomised (1:1:1) to one of three arms (8 patients per arm) with six peptide mass/radioactivity range combinations of 68 Ga-satoreotide trizoxetan.…”

“…1). The administered peptide mass range for all three arms was 5-20 µg on visit 1 (day 1 of the study) and 30-45 µg on visit 2 (day [16][17][18][19][20][21][22]. The radioactivity range was for: All patients had a SSTR agonist PET/CT scan acquired within the previous six months of study enrolment.…”

“…The authors showed that compared with 68 Ga-DOTA-TOC, 68 Ga-satoreotide trizoxetan exhibits substantially higher tumour-to-background ratios and sensitivity for detecting liver metastases [16,17]. Subsequently, a phase II study was conducted to confirm the optimal administered peptide mass and radioactivity of 68 Ga-satoreotide trizoxetan in patients with GEP-NETs [18].…”