NS-17: A PHASE 1 SAFETY AND IMAGING STUDY OF BLZ-100 IN PEDIATRIC BRAIN TUMORS

BACKGROUND: Maximal safe surgical resection is an essential component of pediatric brain tumor treatment. BLZ-100 is an imaging agent consisting of a tumor-binding peptide and the fluorescent molecule indocyanine green which is imaged intraoperatively using a Synchronized Infrared Imaging System (SIRIS). We report the initial experience of BLZ-100 in pediatric brain tumors. METHODS: We conducted a single-institution phase 1 study of BLZ-100 in pediatric patients with the diagnosis of primary brain tumor for whom maximal safe surgical resection was planned. A 3 + 3 dose-escalation design was used. Other key eligibility requirements included normal cardiac, renal, liver and coagulation function. BLZ-100 was administered 2-36 hours prior to planned surgical resection. PK samples were obtained prior, 30 minutes, 2 hours, 4 hours and 2-3 days after administration. Tumor fluorescence was evaluated in situ and ex vivo. RESULTS: 10 subjects of median age 4 years (range 7 months to 14 years) have been treated at 4 dose levels (1.7, 3.5, 6.9, and 13.9 mg/m2), including tumor histology of low-grade glioma (n = 3), ependymoma (n = 3), high-grade glioma (n = 2), ATRT, and medulloblastoma (n = 1 each). No grade 3-4 dose-limiting toxicities related to BLZ-100 administration were observed. Tumor fluorescence was observed in 9 of 10 tumors, oligodendroglioma being the single non-fluorescent tumor. CONCLUSIONS: This is the first prospective trial to evaluate fluorescence-guided neurosurgery in children. BLZ-100 was safe across the dose levels studied to date, and resulted in tumor fluorescence in the majority of tumors evaluated. Further dose levels, PK analysis, and biologic correlative studies are planned.