Phase 2 Clinical Trial of VGT-309 for Intraoperative Molecular Imaging During Pulmonary Resection

Ann Thorac Surg. 2024 May 31:S0003-4975(24)00396-5. doi: 10.1016/j.athoracsur.2024.05.019. Online ahead of print.

Abstract

Background: Advances in intraoperative molecular imaging (IMI) may improve surgical outcomes when resecting tumors in the lung. A single-center trial was conducted using VGT-309, a cathepsin-targeted near-infrared imaging agent that causes lung nodules to fluoresce during surgical resection. The end point of this phase 2 study was to evaluate the frequency that IMI with VGT-309 resulted in a clinically significant event (CSE): localization of pulmonary nodules, discovery of unsuspected additional cancers, or identification of positive margins.

Methods: Patients undergoing surgical resection for known or suspected cancer in the lung received VGT-309 (0.32 mg/kg) preoperatively. During the surgical procedure, localization and resection of the nodules were performed using standard surgical techniques. Near-infrared imaging was then used to localize nodules, seek occult lesions, and assess resection margins. Efficacy was measured by the frequency of CSEs.

Results: Of the 40 patients who underwent pulmonary resection with VGT-309, 17 (42.5%) had at least 1 CSE. Near-infrared imaging identified lesions not found by standard surgical methods in 16 patients, additional cancers not found by preoperative imaging in 1 patient, and margins within 5 mm of the closest staple line in 2 patients. VGT-309 performance was tested across a broad range of tumor types and commercial near-infrared imaging systems. VGT-309 appeared safe, well-tolerated, with no infusion reactions, and no drug-related serious adverse events.

Conclusions: This phase 2 study demonstrated the utility of IMI with VGT-309 in localizing pulmonary nodules, recognizing synchronous lesions, and identifying positive margins. A multi-institutional study will further evaluate the efficacy of VGT-309.