A Prospective, Single-Center, Single-Arm, Exploratory Study of 177Lu-LNC1010 Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors.

Rapid radiopharmaceutical clearance limits the efficacy of peptide receptor radionuclide therapy (PRRT) for the treatment of advanced neuroendocrine tumors (NETs). In this prospective, single-center, single-arm, investigator-initiated trial, we evaluated the safety and efficacy of 177Lu-LNC1010-an optimized, long-acting somatostatin analog-in patients with progressive metastatic NETs. Methods: Twenty-two patients with unresectable, metastatic NETs and disease progression despite treatment with somatostatin analogs or tyrosine kinase inhibitors were enrolled in the study. Participants received up to 4 cycles of PRRT with 177Lu-LNC1010 (3.3 GBq/cycle) at 8-wk intervals. Adverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. The treatment response was evaluated using RECIST 1.1. Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS). Results: The patients (13 men, 9 women; median age, 50.5 y) received 69 PRRT cycles in total. Treatment-related grade 3 or 4 hematologic toxicities were observed in 6 patients (27%). No grade 3 or higher nephrotoxicity or hepatotoxicity was recorded. The median absorbed tumor dose was 2.12 (interquartile range: 1.68-2.96) Gy/GBq. Response after PRRT was assessed in 18 patients. A partial response was achieved in 8 patients (44.0%), stable disease in 9 (50.0%), and progressive disease in 1 (5.6%). The objective response rate was 44.4%, and the disease control rate was 94.4%. After a median follow-up of 21.0 mo, the median PFS was 15.0 mo, and the median OS was not reached. Conclusion: PRRT with 3.3 GBq/cycle of 177Lu-LNC1010 was well-tolerated and exhibited an acceptable safety profile. The objective response rate and disease control rate were high and positively correlated with improved PFS and OS. Appropriate patient selection and earlier intervention may further optimize the therapeutic benefit.