ATNT-16PHASE 1 DOSE ESCALATION AND EXPANSION SAFETY STUDY OF BLZ-100 FOR FLUORESCENCE GUIDED RESECTION OF GLIOMA IN ADULTS

Abstract

BLZ-100 is an intraoperative, fluorescent near-infrared imaging agent designed to specifically label tumor tissue and enable more complete surgical resection. The chlorotoxin(CTX) peptide portion of BLZ-100 targets the tumor, and the coupled fluorescent dye, indocyanine green, provides the fluorescent signal. CTX has been shown to target brain cancer in humans and BLZ-100 uptake has been shown in animal tumor models. This study characterizes the safety and fluorescence imaging potential of BLZ-100 in subjects with newly diagnosed or recurrent glioma. BLZ-100 is given as a slow bolus IV injection approximately 1 day before neurosurgery. Adequate bone marrow, liver and kidney function are required to participate. Dose escalation utilized a “3 + 3” design with 3 pre-specified dose levels. Dose limiting toxicity is defined as any related adverse event (AE) of ≥ Grade 3 severity occurring within 7 days of BLZ-100 administration. Safety measures include adverse events, laboratory measures of hematology, liver and kidney function, vital signs and electrocardiograms (ECG). Fluorescent images in situ are taken prior to and at the completion of tumor resection. Portions of excised tumor are also imaged ex vivo. Three subjects received 3 mg BLZ-100 in the first cohort; four subjects received 9 mg in the second. No dose limiting toxicity or BLZ-100 related adverse events have been observed. Two subjects had pathologically confirmed Grade II tumors, two had Grade III, and three had Grade IV. Two of the 7 cases were newly diagnosed. Fluorescent signal from portions of the resected tumor has been observed using ex vivo techniques and was concordant with pathology confirmed tumor. In situ imaging has been achieved in two cases with readily accessible tumors. These data suggest BLZ-100 is well tolerated and tumor-specific fluorescence can achieved in vivo. Dose escalation is continuing to 18 mg.