ACTR-49. PHASE 1 SAFETY STUDY OF BLZ-100 FOR FLUORESCENCE-GUIDED RESECTION OF GLIOMA IN ADULT SUBJECTS

Abstract

Real time, fluorescence-guided resection (FGS) of brain cancer may improve extent of resection while minimizing brain injury. BLZ-100 is a near-infrared (NIR) imaging agent composed of the tumor-targeting peptide, chlorotoxin and the NIR fluorescent dye, indocyanine green. It has the potential to selectively label brain and other tumors. This Phase 1 dose escalation study characterized the safety and fluorescence imaging of BLZ-100 in adults with newly diagnosed or recurrent glioma. An IV injection was given before surgery (range 3 -29 hours). Dose escalation utilized a “3+3” design with 5 pre-specified dose levels. Dose limiting toxicity (DLT) was defined as any ≥ Grade 3 BLZ-100 related adverse event (AE) within 7 days of dosing. Safety measures included AEs, laboratory measures, vital signs, and electrocardiograms. Fluorescent images were taken before and after resection (in situ) and of excised tissue (ex vivo) using a NIR camera system suitable for surgery. A total of 17 subjects were enrolled and received doses from 3 to 30 mg. No DLT was observed and none of the treatment-emergent AEs were associated with BLZ-100 dosing. There were 9 cases with WHO Grade III and IV disease and 8 with WHO grade I and II. Fluorescent signal in excised tumor samples increased with increasing dose, with robust fluorescence noted consistently at doses ≥18 mg. Fluorescence was noted in both early (day of) and late (next day) interval (time between imaging and excision) cases, however, the earlier time interval appeared better. Cases with high grade disease had more subjects positive (7/9) and more intense signal compared to those with low grade disease (3/8) based on both in situ and ex vivo imaging. The location of fluorescent signal in excised specimen was concordant with pathology confirmed tumor. These data support the potential use of BLZ-100 for FGS of gliomas.