Cancer Res Treat.  2023 Jan;55(1):334-343. 10.4143/crt.2021.1022.

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

• Ryoo HG
• Suh M
• Kang KW
• Lee DW
• Han SW
• Cheon GJ

• KMID: 2538016
• DOI: http://doi.org/10.4143/crt.2021.1022

Abstract

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) ¹⁷⁷Lu-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 ¹⁷⁷Lu-labeled DOTATATE, as a potentially safe and efficacious treatment option for NET patients in Korea.

Keyword

SNU-KB-01; Lu-DOTATATE; No-carrier added; Neuroendocrine tumors; Peptide receptor radionuclide therapy

Figure

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  Fig. 1 Study design of peptide receptor radionuclide therapy with SNU-KB-01. DLT, dose-limiting toxicity.

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  Fig. 2 Representative 177Lu-DOTATATE whole-body planar scans of a patient with rectal neuroendocrine tumor with multiple metastases in liver, lymph nodes, bones at 4, 24, 48, and 120 hours after administration of SNU-KB-01.

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  Fig. 3 Changing trend of mean Common Terminology Criteria for Adverse Events (CTCAE) grade value (A), hemoglobin (B), platelet (C), white blood cell (WBC) counts (D) for hematologic toxicity after cycles of SNU-KB-01. The trend of the progressive decline of hematological parameters was observed during the treatment cycles.

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  Fig. 4 Percent changes in the sum of diameters of target lesions from baseline during peptide receptor radionuclide therapy with SNU-KB-01.

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  Fig. 5 68Ga-DOTATOC positron emission tomography (PET)/computed tomography (CT), contrast-enhanced liver CT, and 177Lu-DOTATATE whole-body planar scan in a 52-year-old man with rectal neuroendocrine tumor and multiple metastases in liver, lymph nodes, and bones. He had a partial response (–46.3%) after the treatment with four cycles of SNU-KB-01.

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  Fig. 6 Kaplan-Meier curve of progression-free survival after the first cycle of SNU-KB-01.

Reference

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