Yamada Miko, Miller Dennis M, Lowe Melinda, Rowe Casey, Wood Dominic, Soyer H Peter, Byrnes-Blake Kelly, Parrish-Novak Julia, Ishak Laura, Olson James M, Brandt Gordon, Griffin Paul, Spelman Lynda, Prow Tarl W
The University of Queensland Diamantina Institute, The University of Queensland, Dermatology Research Centre, Brisbane, Queensland, Australia.
Blaze Bioscience, Inc., Seattle, WA, USA.
Contemp Clin Trials Commun. 2021 Aug 4;23:100830. doi: 10.1016/j.conctc.2021.100830. eCollection 2021 Sep.
BLZ-100 (tozuleristide) is an intraoperative fluorescent imaging agent that selectively detects malignant tissue and can be used in real time to guide tumor resection. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of BLZ-100 and to explore the pharmacodynamics of fluorescence imaging of skin tumors. In this first-in-human study, BLZ-100 was administered intravenously to 21 adult patients 2 days before excising known or suspected skin cancers. Doses were 1, 3, 6, 12, and 18 mg, with 3-6 patients/cohort. Fluorescence imaging was conducted before and up to 48 h after dosing. BLZ-100 was well tolerated. There were no serious adverse events, deaths, or discontinuations due to adverse events, and no maximum tolerated dose (MTD) was identified. Headache (n = 2) and nausea (n = 2) were the only BLZ-100 treatment-related adverse events reported for >1 patient. Median time to maximal serum concentration was <0.5 h. Exposure based on maximal serum concentrations increased in a greater than dose-proportional manner. For intermediate dose-levels (3-12 mg), 4 of 5 basal cell carcinomas and 4 of 4 melanomas were considered positive for BLZ-100 fluorescence. BLZ-100 was well tolerated at all dose levels tested and these results support further clinical testing of this imaging agent in surgical oncology settings. Clinicaltrials.gov: NCT02097875.
BLZ-100（tozuleristide）是一种术中荧光成像剂，可选择性检测恶性组织，并可实时用于指导肿瘤切除。本研究的目的是评估BLZ-100的安全性、耐受性和药代动力学，并探索皮肤肿瘤荧光成像的药效学。在这项首次人体研究中，在切除已知或疑似皮肤癌前两天，对21名成年患者静脉注射BLZ-100。剂量分别为1、3、6、12和18毫克，每组3至6名患者。在给药前及给药后长达48小时进行荧光成像。BLZ-100耐受性良好。没有严重不良事件、死亡或因不良事件而停药的情况，也未确定最大耐受剂量（MTD）。头痛（n = 2）和恶心（n = 2）是报告的仅有的与BLZ-100治疗相关且有超过1名患者出现的不良事件。达到最大血清浓度的中位时间<0.5小时。基于最大血清浓度的暴露以大于剂量比例的方式增加。对于中等剂量水平（3 - 12毫克），5例基底细胞癌中有4例以及4例黑色素瘤中有4例被认为BLZ-100荧光呈阳性。在所有测试剂量水平下，BLZ-100耐受性良好，这些结果支持在外科肿瘤学环境中对该成像剂进行进一步的临床试验。Clinicaltrials.gov：NCT02097875。
