Phase 1 Study of No-Carrier Added (177)Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor–Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea

PURPOSE: To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) (177)Lu-labeled DOTATATE. MATERIALS AND METHODS: Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.55 GBq (n=3) and 7.40 GBq (n=4). We assessed the incidence of dose-limiting toxicity (DLT) and adverse event, absorbed dose of kidneys and bone marrow, and objective tumor response. RESULTS: Seven patients completed 4 cycles (21.3–30.1 GBq total dose) of SNU-KB-01. The mean absorbed doses to kidneys and bone marrow were 0.500 mGy/MBq and 0.053 mGy/MBq, respectively, and the total body effective dose was 0.115 mSv/MBq. No DLT was observed and the maximum tolerated dose was 7.40 GBq/cycle. Grade 3 thrombocytopenia occurred in one patient, but no other grade 3 or 4 major hematologic or renal toxicity was observed. The best objective response to SNU-KB-01 was partial response. Overall response rate was 42.9% and disease control rate was 85.7%. CONCLUSION: Treatment with 4 cycles of SNU-KB-01 was well tolerated and resulted in control of disease in most of the patients. Our results indicate SNU-KB-01, an NCA (177)Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.