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A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer

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机构： [1]Department of Nuclear Medicine, the First Afliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China [2]Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Afliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China [3]Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China [4]Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore [5]Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore [6]Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore [7]Department of Nuclear Medicine, the Afliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China [8]Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Sichuan Province, Luzhou 646000, China [9]Institute of Nuclear Medicine, Southwest Medical University, Luzhou 646000, Sichuan Province, China [10]Academician (Expert) Workstation of Sichuan Province, Luzhou 646000, Sichuan Province, China [11]Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, First Afliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China [12]Fujian Key Laboratory of Precision Medicine for Cancer, the First Afliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China [13]Departments of Surgery, Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore [14]Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore [15]Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos 138673, Singapore, Singapore

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关键词： Radioligand therapy [177Lu]Lu-LNC1003 Metastatic castration-resistant prostate cancer (mCRPC) Phase 1 Albumin binding

摘要：

This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of 177Lu-PSMA-EB-01 (denoted as [177Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC).A total of 13 patients with mCRPC were recruited in this study. A standard 3 + 3 dose escalation protocol was performed. The following dose levels were ultimately evaluated: 1.11, 1.85, and 2.59 GBq/cycle. Patients received [177Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval.Patients received fractionated doses of [177Lu]Lu-LNC1003 ranging from 1.11 to 2.59 GBq per cycle. Myelosuppression was dose-limiting at 2.59 GBq, and 1.85 GBq was determined to be the MTD. The total-body effective dose for 177Lu-LNC1003 was 0.35 ± 0.05 mSv/MBq. The salivary glands were found to receive the highest estimated radiation dose, which was calculated to be 3.61 ± 2.83 mSv/MBq. The effective doses of kidneys and red bone marrow were 1.88 ± 0.35 and 0.22 ± 0.04 mSv/MBq, respectively. The tumor mean absorbed doses for bone and lymph node metastases were 8.52 and 9.51 mSv/MBq. Following the first treatment cycle, PSA decline was observed in 1 (33.3%), 4 (66.7%), and 2 (50.0%) patients at dose levels 1 (1.11 GBq), 2 (1.85 GBq), and 3 (2.59 GBq), respectively. Compared with the baseline serum PSA value, 1 (33.3%) at dose level 1 and 4 (66.6%) patients at dose level 2, presented a PSA decline after the second treatment cycle.This phase 1 trial revealed that the MTD of [177Lu]Lu-LNC1003 is 1.85 GBq. The treatment with multiple cycles at the dose of 1.11 GBq /cycle and 1.85 GBq /cycle was well tolerated. [177Lu]Lu-LNC1003 has higher tumor effective doses in bone and lymph nodes metastases while the absorbed dose in the red bone marrow should be closely monitored in future treatment studies with higher doses and multiple cycles. The frequency of administration also needs to be further explored to assess the efficacy and side effects of [177Lu]Lu-LNC1003 treatment.177Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic.gov/ct2/show/NCT05613738.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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第一作者：

第一作者机构： [1]Department of Nuclear Medicine, the First Afliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China [2]Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Afliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China

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通讯机构： [1]Department of Nuclear Medicine, the First Afliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China [2]Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Afliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China [4]Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore [5]Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore [6]Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore [12]Fujian Key Laboratory of Precision Medicine for Cancer, the First Afliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China [13]Departments of Surgery, Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore [14]Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore 117597, Singapore [15]Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos 138673, Singapore, Singapore

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A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [177Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer

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