A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients
Miko Yamada, Dennis M Miller, Melinda Lowe, Casey Rowe, Dominic Wood, H Peter Soyer, Kelly Byrnes-Blake, Julia Parrish-Novak, Laura Ishak, James M Olson, Gordon Brandt, Paul Griffin, Lynda Spelman, Tarl W Prow, Miko Yamada, Dennis M Miller, Melinda Lowe, Casey Rowe, Dominic Wood, H Peter Soyer, Kelly Byrnes-Blake, Julia Parrish-Novak, Laura Ishak, James M Olson, Gordon Brandt, Paul Griffin, Lynda Spelman, Tarl W Prow
Abstract
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.
Keywords: CTX, chlorotoxin; Cystine-knot miniproteins; Fluorescent dyes; NCI CTCAE, National Cancer Institute's Common Terminology Criteria for Adverse Events; NMSC, non-melanoma skin cancer; PK, pharmacokinetic(s); Skin neoplasms.
Conflict of interest statement
DMM, JPN, and LI are employees or former employees of and hold equity in Blaze Bioscience, Inc. ML, KBB, and GB are consultants for Blaze Bioscience, Inc. and Blaze Bioscience Australia Pty Ltd. JMO is a co-founder of and holds equity in Blaze Bioscience, Inc. LS was a paid clinical investigator on the trial. HPS is a shareholder of MoleMap NZ Limited and e-derm consult GmbH and undertakes regular teledermatological reporting for both companies. HPS is a Medical Consultant for Canfield Scientific Inc., MetaOptima and Revenio Research Oy and also a Medical Advisor for First Derm.
© 2021 The Authors.
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Source: PubMed