DISCO: Diagnostic performance of ⁶⁴ Cu-SARTATE compared to ⁶⁸ Ga-DOTATATE in patients with known or suspected neuroendocrine tumors with focus on liver findings.

Abstract

618 Background: Diagnostic imaging is critical in the theranostic management of neuroendocrine tumors (NETs). 64 Cu-SARTATE may provide advantages over existing imaging agents due to its longer half-life and sarcophagine chelator, with a potential to accurately detect additional disease in NETs. Methods: This multi-center Phase II study assessed the safety and efficacy of 64 Cu-SARTATE (200 MBq) in participants with known or suspected gastroenteropancreatic (GEP)-NETs (NCT04438304). Standard of care 68 Ga-DOTATATE PET/CT (DOTATATE) was performed within 35 days prior to 64 Cu-SARTATE PET/CT (SARTATE; at 4 ± 1 hrs [same-day imaging] and 20 ± 4 hrs [next-day imaging] post-injection). Scans were assessed by two independent blinded central readers, and every abnormal focus (an abnormality that may be related to a GEP-NET and cannot be accounted for by a benign process) was recorded. Discordant lesions present on only one of the two PET scans (either DOTATATE or SARTATE) were subsequently evaluated by an independent assessor against a standard of truth (SOT; biopsy and/or follow-up conventional imaging). The per-lesion sensitivity for discordant lesions was calculated for both SARTATE and DOTATATE (defined as the proportion of true positive foci / [true positive foci + false negative foci]; primary endpoint). Values express the averages across readers and both PET/CT time points (for SARTATE). Safety was monitored using safety parameters typical of early phase trials. Results: 45 participants were enrolled and received SARTATE (41 known NETs and 4 suspected NETs). Most subjects had stage 3 or 4 disease. The mean number of foci detected by SARTATE was 441 vs. 227 by DOTATATE. A total of 238 discordant foci were identified in 34 subjects with scan pairs; 223 of these were detected by SARTATE alone and 15 by DOTATATE alone. For the 122 discordant foci with evaluable SOT, the difference in sensitivity for SARTATE vs. DOTATATE was statistically significant (94.7% [95% CI 65.1, 99.5] for SARTATE vs. 5.4% [95% CI 0.5, 34.9] for DOTATATE; p<0.001). The liver had the highest number of foci detected by both tracers (352 foci on SARTATE vs. 180 on DOTATATE) among all sites. Seven (15.6%) participants experienced 9 SARTATE-related AEs; 8 were Grade 1 and one was Grade 2, with most resolving within 2 days. Conclusions: 64 Cu-SARTATE was found to be safe and well-tolerated in patients with GEP-NETs. 64 Cu-SARTATE lesion detection was numerically higher than that of 68 Ga-DOTATATE, with the liver having the highest number of lesions identified. SARTATE was able to detect additional true positive lesions compared to DOTATATE. The enhanced diagnostic performance offered by 64 Cu-SARTATE, especially in key organs affected by GEP-NETs, may have important clinical implications to inform treatment decisions. A phase III study of 64 Cu-SARTATE in GEP-NETs is being planned. Clinical trial information: NCT04438304 .