Multi-Institutional Phase 2 Clinical Trial of Intraoperative Molecular Imaging of Lung Cancer

Abstract Background Intraoperative molecular imaging (IMI) may improve surgical outcomes during pulmonary resection for lung cancer. A multi-institutional Phase 2 IMI clinical trial was conducted utilizing a near-infrared (NIR), folate-receptor targeted contrast agent for lung adenocarcinomas, OTL38. The primary goal was to determine if OTL38 improved surgeons’ ability to identify hard-to-find nodules, occult cancers, and positive margins. Methods Patients with lung nodules received OTL38 (0.025mg/kg) preoperatively. Patients had IMI sequentially during lung inspection, tumor resection, and margin check. Efficacy was evaluated by occurrence of clinically significant events (CSE), occurrences that caused the surgeon to modify the operation or up-stage the patient’s cancer. Safety was assessed for single intravenous dose of OTL38. Results Of 110 patients recruited; 92 were eligible for analysis. During Lung Inspection, IMI found 24 additional nodules, 9 (10%) of which were cancers that had not been known preoperatively. During Tumor Resection, IMI located 11 (12%) lesions that the surgeon could not find. During Margin Check, IMI revealed 8 positive margins (9%) that the surgeon thought was negative. Benefits of IMI were pronounced in patients undergoing sublobar pulmonary resections and in those with ground-glass opacities. There were no serious adverse events. All surgeons felt comfortable with the procedures by 10 cases. Conclusions In this Phase 2 clinical trial, IMI improved outcomes for 26% of patients. A randomized, multi-institutional Phase 3 clinical trial is underway.