A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients

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.

Current Status of Peptide Medications and the Position of Active Therapeutic Peptides with Scorpion Venom Origin

“…A preclinical test also validated the utility of BLZ-100 in providing contrast for imaging canine adenocarcinomas, squamous cell carcinomas, and mast cell tumors (52). The CTX is attractive as a targeted imaging agent for cancer because of these unique properties (56). BLZ-100 is undergoing human clinical trials and has shown negligible toxicity in humans in all clinical trials conducted to date (56,57).…”

Phage Particles of Controlled Length and Genome for In Vivo Targeted Glioblastoma Imaging and Therapeutic Delivery

“…Several peptides have demonstrated BBB shuttling properties including GL1, SGV, PepTGN, PepC7, and angiopep-2, among others . However, CTX remains currently the only FDA-approved ligand for use in glioma surgeries and has recently shown promise in directing immunotherapies to orthotopic intracranial xenografts of GBM. ,− …”

Intraoperative Tumor Detection Using Pafolacianine

“…Three of these novel probes (BLZ 100, LUM 015, and SGM-101) have reached phase III clinical trials and are expected to be approved by the FDA in a couple of years [ 95 , 96 ]. BLZ 100, used for real-time tumor detection during brain and breast cancer surgeries, consists of a natural chlorotoxin peptide, which targets the protein components of cholesterol-rich lipid rafts from cancer lesions [ 97 ]. LUM 015 contains a Cy5 fluorophore linked to a cathepsin activatable peptide, being used in combination with the LUM imaging system for fluorescent-guided surgery in residual breast cancer, gastrointestinal cancer, and prostate cancer [ 98 ].…”