Improving lung cancer surgery with an intraoperative, tumor-targeted, activatable fluorescent imaging agent

PROJECT SUMMARY/ABSTRACT More than 228,000 people in the United States will receive a lung cancer diagnosis this year. Only 14%-49% of early-stage patients survive at least 5 years after their diagnosis, and the survival rates fall below 5% for patients with advanced-stage IIIB or IV. Tumor recurrence after resection is a critical factor influencing these poor prognoses. If any cancerous tissue is left behind during surgery, the risk of an aggressive tumor recurrence increases dramatically. These recurrent tumors rapidly spread and negatively impact a patient’s clinical outlook. Therefore, accurately identifying tumor tissue during surgical resection is crucial. Despite this need, translating preoperative images into the surgical suite for real-time, precise visualization remains a challenge; in an intraoperative setting for lung cancer, tissues are often displaced, lungs are deflated, and blood can obscure the surgical field. Vergent Bioscience, Inc. developed a molecular imaging agent, VGT-309, to meet this urgent need for improved intraoperative visualization of tumors. This agent is administered as a single intravenous dose prior to surgery, after which it will bind to upregulated cathepsins in the cancerous tissue, become activated, and fluoresce. Commercially available near-infrared (NIR) imaging systems can then be used during surgery to illuminate the tumor and enable surgeons to precisely identify and remove tumor margins, ensuring no cancerous tissue is left behind. VGT-309 has a wide post-dose imaging window and can be seamlessly integrated into existing surgical workflows without requiring additional training or equipment. Extensive preclinical safety, efficacy, and dosing studies have validated the use of VGT-309 to facilitate the resection of a variety of solid tumor types. A Phase 1 randomized, double-blind, placebo-controlled, single ascending dose study in healthy subjects was completed in early 2021 to evaluate the safety, tolerability, and pharmacokinetics of VGT-309. All four doses were safe and well-tolerated during this trial, so a starting dose of 0.05mg/kg was selected for patients with lung cancer who are currently enrolled in an ongoing Phase 2 clinical trial in Australia to determine optimal VGT-309 dose and timing. During the present Direct to Phase II application, Vergent will 1) manufacture VGT-309 drug product following Current Good Manufacturing Practices, and 2) collaborate with the Hospital of the University of Pennsylvania to evaluate this agent in a Phase 2, open-label study to assess its safety, tolerability, and efficacy in 35 patients scheduled to undergo standard of care surgical resection for suspected or proven lung cancer. Once successfully validated in our Phase 2 clinical trial, VGT-309 will be evaluated in larger, multi-site Phase 2b and Phase 3 studies. Ultimately, we plan to expand the use of this fluorescent, activatable molecular imaging agent to other solid tumors such as colorectal, head and neck, ovarian, brain, gastric, and breast. This agent has the potential to transform the surgical oncology space and optimize clinical outcomes for patients undergoing resection of tumors.