A phase II/III randomized, blinded study of tozuleristide for fluorescence imaging detection during neurosurgical resection of pediatric primary central nervous system (CNS) tumors: PNOC012 (Pacific Pediatric Neuro-oncology Consortium).

TPS2575 Background: Tozuleristide (also known as BLZ-100 or Tumor Paint) is a fluorescent imaging drug designed to specifically label and accumulate in tumor tissue, thus enabling more precise surgical tumor resection intraoperatively. Tozuleristide achieves tumor targeting through the peptide portion of the molecule, a modified chlorotoxin peptide, and its imaging properties from a coupled near-infrared fluorescent dye, an indocyanine green. Tozuleristide has been studied in 4 Phase 1 studies, including a trial in pediatric brain cancer subjects. No tozuleristide SAEs or dose limiting toxicity were observed in the 97 subjects treated in the Phase 1 program at doses up to 30 mg in adults or 17.3 mg/m2 in pediatrics (Hansen S et al, WMIC 2018, P196). Eighty percent of pediatric subjects receiving tozuleristide had tumors considered fluorescence positive, including high and low grade glioma, ependymoma, and medulloblastoma. Methods: This study randomizes subjects in a 1:10 ratio to standard of care or tozuleristide arms. The primary efficacy objectives and endpoints are based on equivocal regions of tissue encountered in surgery. Prior to fluorescence assessment, the surgeon assesses the suspected nature of the tissue (more likely tumor/less likely tumor). Tissue specimens of equivocal regions are collected for blinded central pathology assessment. Sensitivity and specificity of the surgeon’s designation, fluorescence assessment, and ratios of surgeon to fluorescence assessments comprise the primary efficacy analyses. Tozuleristide is given as an IV bolus dose of 15 mg/m2 to pediatric subjects 1 to 36 hours prior to surgery. Subjects must have a MRI documented lesion consistent with a CNS tumor for which resection is planned. Measures of safety include adverse events, laboratory measures of hematology, liver and kidney function and changes in vital signs and ECGs. Pharmacokinetic blood samples are collected up to 3 hr post dose. Fluorescence imaging is assessed during surgery using an investigational “Canvas System” imaging device attached to a surgical microscope. Collected pathology specimens will also be subjected to further genetic, molecular and pathology studies, including fluorescence assessment of frozen tissue sections. SAEs and patient reported outcomes are collected for 3 months. The SMC for the study last reviewed the data for this study in July 2019 and recommended the trial continue as planned. Clinical trial information: NCT03579602 .