一项评估 [Lu]Lu-LNC1003 在转移性去势抵抗性前列腺癌患者中的最大耐受剂量和患者特异性剂量学的 1 期临床试验。
A phase 1 trial to determine the maximum tolerated dose and patient-specific dosimetry of [Lu]Lu-LNC1003 in patients with metastatic castration-resistant prostate cancer.
机构信息
Department of Nuclear Medicine, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.
Department of Nuclear Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, Fujian Province, China.
出版信息
Eur J Nucl Med Mol Imaging. 2024 Feb;51(3):871-882. doi: 10.1007/s00259-023-06470-3. Epub 2023 Oct 21.
PURPOSE
This translational study aimed to determine the maximum tolerated dose (MTD), safety, dosimetry, and therapeutic efficacy of Lu-PSMA-EB-01 (denoted as [Lu]Lu-LNC1003) in patients with metastatic castration-resistant prostate cancer (mCRPC).
METHODS
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 [Lu]Lu-LNC1003 therapy for up to two cycles at a 6-week interval.
RESULTS
Patients received fractionated doses of [Lu]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 Lu-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.
CONCLUSION
This phase 1 trial revealed that the MTD of [Lu]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. [Lu]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 [Lu]Lu-LNC1003 treatment.
TRIAL REGISTRATION
Lu-PSMA-EB-01 in patients with metastatic castration-resistant prostate cancer (NCT05613738, Registered 14 November 2022). URL of registry https://classic.
CLINICALTRIALS
gov/ct2/show/NCT05613738.
目的
本转化研究旨在确定 Lu-PSMA-EB-01（标记为 [Lu]Lu-LNC1003）在转移性去势抵抗性前列腺癌（mCRPC）患者中的最大耐受剂量（MTD）、安全性、剂量学和治疗效果。
方法
本研究共纳入 13 例 mCRPC 患者。采用标准的 3+3 剂量递增方案。最终评估了以下剂量水平：1.11、1.85 和 2.59GBq/周期。患者每 6 周接受一次 [Lu]Lu-LNC1003 治疗，最多进行两个周期。
结果
患者接受了 1.11 至 2.59GBq 不等的分次剂量[Lu]Lu-LNC1003。2.59GBq 时出现骨髓抑制，1.85GBq 确定为 MTD。Lu-LNC1003 的全身有效剂量为 0.35±0.05mSv/MBq。唾液腺接收到的估计辐射剂量最高，为 3.61±2.83mSv/MBq。肾脏和红骨髓的有效剂量分别为 1.88±0.35 和 0.22±0.04mSv/MBq。骨和淋巴结转移的肿瘤平均吸收剂量分别为 8.52 和 9.51mSv/MBq。第一个治疗周期后，1 例（33.3%）、4 例（66.7%）和 2 例（50.0%）患者在剂量水平 1（1.11GBq）、2（1.85GBq）和 3（2.59GBq）中观察到 PSA 下降。与基线血清 PSA 值相比，1 例（33.3%）在剂量水平 1 和 4 例（66.6%）在剂量水平 2 的患者在第二个治疗周期后 PSA 下降。
结论
这项 1 期试验表明，[Lu]Lu-LNC1003 的 MTD 为 1.85GBq。以 1.11GBq/周期和 1.85GBq/周期的多个周期治疗耐受性良好。[Lu]Lu-LNC1003 在骨和淋巴结转移中具有更高的肿瘤有效剂量，而在未来更高剂量和多个周期的治疗研究中，应密切监测红骨髓的吸收剂量。给药频率也需要进一步探讨，以评估 [Lu]Lu-LNC1003 治疗的疗效和副作用。
试验注册
Lu-PSMA-EB-01 在转移性去势抵抗性前列腺癌患者中的研究（NCT05613738，2022 年 11 月 14 日注册）。网址：https://classic.
临床试验
gov/ct2/show/NCT05613738.
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