SURG-15. A Phase II investigator initiated study to evaluate a glioma specific fluorescence imaging agent tozuleristide and Canvas Imaging System to aid the resection of gliomas in adults

Abstract Adult patients with newly diagnosed suspected, or previously resected, high- or low-grade CNS tumors received a single dose (24 or 36 mg) of tozuleristide 3-29 hours before surgery. All patients with gadolinium-enhancing tumor, consisting of 27 glioblastomas, one grade 3 astrocytoma, and one grade 2 astrocytoma received 24 mg of tozuleristide. The Canvas imaging system was used intraoperatively to visualize tumor fluorescence. The protocol specified that the surgeon would biopsy regions of interest (ROI) that were identified under white light as definite tumor or peripheral tissue. Intraoperative fluorescence assessments of these ROIs were obtained and compared to post-operative tissue biopsy histopathology to determine tozuleristide diagnostic performance. Extent of resection (EOR) calculated from pre- and post-operative MRI was compared to matched historical controls. 33 subjects who underwent all study procedures. 26/29 gadolinium-enhancing tumors displayed fluorescence. In gadolinium-enhancing tumors, a total of 169 tissue biopsies were obtained yielding Sensitivity and Positive Predictive Value (PPV) of 85.5% and 73.5%. 93% (12/13) of subjects with fluorescence in the resection bed at completion of maximal safe resection had tumor remaining on post-operative MRI, all in areas unsafe for further resection. Residual fluorescence moderately correlated with lower EOR (r=-0.26). 12/13 subjects with residual fluorescence had tumor remaining, all in areas unsafe for further resection. Average EOR was 92.04% (TOZU) and 90.88% (controls). Among patients with grade IV glioblastoma, TOZU patients undergoing repeat resection had significantly higher rate of GTR (>98% resection) (6/10 versus 2/11 in controls, p<1e-6), but those undergoing initial resection had significantly lower GTR rate (5/18 versus 10/20, p<0.01). Length of hospital stay was shorter in TOZU patients (p<0.05) and clinical outcomes such as AEs were not significantly different. Tozuleristide fluorescence was predictive of and sensitive for tumor, indicating its good potential as an FGS imaging agent for glioma resection in adult high-grade tumors.