Lung cancer remains the leading cause of cancer-related deaths worldwide. Surgical removal of the tumor is the best therapeutic options for patients with non-small cell lung cancer, yet up to 20% of patients still leave the operating room with deposits of cancer left behind. Advances in CAT and PET scans have provided surgeons with helpful radiographic imaging information prior to surgery, but have limited specificity for nodules less than 5-7mm in diameter. Subsequent pathological analysis confirms/refutes what a surgeon has resected. However, both of these procedures require additional time and occur outside of the operating room, providing little real-time support during the surgery. The applicant has developed a novel cocktail (OTL489) that combines two ligands targeted specifically to lung tumor tissue tagged with a near infrared (NIR) dye (OTL38+OTL338). The fluorescent cocktail containing ligands targeted to both folate and the CA IX receptors will essentially identify tumor populations that overexpress either or both of these cell surface receptors. Real-time visualization not only of the complete tumor margins but also potentially other malignant sites outside the primary tumor area will enable complete surgical removal of primary and other tumor tissues. Moreover, fluorescence imaging could aid in the surgical decision to conserve lung function by removing only the diseased tumor tissue rather than lobectomy or pneumonectomy. During Phase II, OTL will perform a critical proof of concept study that will extend prior studies using components of the cocktail, alone and in combination, and validate continued development toward an Investigational New Drug (IND) application. First, OTL will optimize the manufacturing of OTL338. Pre- pharmacological studies will then be conducted in small animals to determine the optimum dose, imaging time, tumor-to-background ratio, etc. of OTL338 to be used in the IND-enabling studies. OTL will manufacture OTL338 (non-GMP), 13C-OTL338, and 13C-OTL38 in-house for the IND-enabling safety and pharmacology toxicity studies that will be conducted at Charles River Laboratories (CRL). Similarly, following the optimization of formulation and drug-drug interaction and pre-pharmacological studies of the cocktail (OTL489), IND-enabling bridging toxicity studies for the cocktail will be conducted in rodent and non-rodent species at CRL. The ultimate goal will be to finish non-GMP manufacturing and IND-enabling studies to file the IND application for the Phase 1 first in human study of the cocktail. Commercialization efforts will be aimed at the development of the cocktail for intraoperative use in lung cancer resection surgery that will enable more complete tumor removal and a reduction in the recurrence rate of pulmonary cancer and its associated morbidity, mortality, and expense.
Lung cancer remains a leading cause of cancer-related deaths worldwide. Surgical resection is the best therapeutic option for patients with non-small cell lung cancer (NSCLC). However, survival rates are directly affected by incomplete removal of the primary tumor and other malignant sites that cannot be identified. The applicant is developing a cocktail of two ligands attached to a fluorescent dye that will be specifically targeted to tumor surface receptors that will visualize and enable image-guided resection of NSCLC, representing a significant advancement over current surgical limitations in pulmonary resection.
