SBIR-STTR Award

Significance Lung cancer is the leading cause of cancer mortality with a 5-year survival rate of less than 20% following standard of care therapy. Problem Despite the use of aggressive surgery, combination chemotherapy and immunotherapy, a major limitation in the control of primary and metastatic non-small cell pulmonary tumors with the use of the systemic administration of drugs is the low drug concentration in the lungs due to blood volume dilution and metabolism. There is a critical unmet medical need to develop new strategies to improve patient treatment outcomes. Innovation In contrast to systemic delivery of chemotherapy, inhalation delivers a chemotherapeutic drug directly to tumor tissues in the lung thereby enhancing its efficacy and safety due to increased local drug concentration in the lung, decreased systemic drug levels in the circulation, and decreased systemic toxicity. Gap Preliminary pre-clinical in-vivo studies using nebulized chemotherapy drugs has demonstrated efficacy and established the feasibility of delivery via aerosol, but nebulization of toxic drugs has major drawbacks. These drawbacks include a lack of efficient peripheral airway penetration, high mouth-throat deposition, contamination of equipment, and collateral aerosol risk to medical staff. Objective To address these drawbacks, we are developing a new method of delivering a chemotherapeutic drug via inhalation to reach pulmonary tumors directly in order to maximize the effectiveness and safety of the aerosol treatment with a fraction of the standard dose. We will create a novel dry powder chemotherapeutic formulation containing an FDA approved chemotherapy medication for the treatment of non-small cell lung cancer. Aims Aims of this proposal will be 1) scale-up the lead Quench EEG formulation and conduct characterization, stability, and performance studies, and 2) conduct IND-enabling toxicology studies in an established inhalation toxicology rodent model for regulatory submission. Commercial Potential Translation of this technology into a clinically beneficial inhalable chemotherapy product has the potential to significantly improve the treatment of pulmonary tumors in lung cancer patients by delivering targeted lower doses of medicine directly to the lung while minimizing systemic toxicity.

Public Health Relevance Statement:
Project Narrative Lung cancer is the leading cause of cancer mortality with a 5-year survival rate of less than 20% following standard of care treatment. There is strong evidence that targeted delivery of inhaled chemotherapy medication to the lung at a fraction of the current dose will have a major impact on increasing survival and reducing lung tumor burden in lung cancer patients with far less side effects than those associated with current systemic intravenous chemotherapy. Based on preliminary data, we will develop a novel inhaled chemotherapy treatment in order to directly target pulmonary tumors in order to improve survival in lung cancer patients.

Project Terms:
Aerosols; Blood Volume; Non-Small-Cell Lung Carcinoma; NSCLC; NSCLC - Non-Small Cell Lung Cancer; Non-Small Cell Lung Cancer; Nonsmall Cell Lung Carcinoma; Cells; Cell Body; Clinical Research; Clinical Study; Pharmacotherapy; Drug Therapy; drug treatment; Combination Drug Therapy; Polychemotherapy; combination chemotherapy; combination pharmacotherapy; combined drug therapy; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Investigational Drugs; Investigational New Drugs; Electroencephalography; EEG; Electroencephalogram; Elements; Equipment Contamination; Excipients; Growth; Generalized Growth; Tissue Growth; ontogeny; Human; Modern Man; Immunotherapy; Immune mediated therapy; Immunologically Directed Therapy; immune therapeutic approach; immune therapeutic interventions; immune therapeutic regimens; immune therapeutic strategy; immune therapy; immune-based therapies; immune-based treatments; immuno therapy; In Vitro; Inhalators; Inhaler; Lead; Pb element; heavy metal Pb; heavy metal lead; Leucine; Lung; Lung Respiratory System; pulmonary; Lung Neoplasms; Lung Tumor; Pulmonary Neoplasms; Medical Staff; Medicine; Metabolism; Intermediary Metabolism; Metabolic Processes; Methods; mortality; United States National Institutes of Health; NIH; National Institutes of Health; Nebulizer; nebulization; nebulize; Patients; Pharyngeal structure; Pharynx; Throat; Powder dose form; Powders; Production; Research; Risk; Rodent; Rodentia; Rodents Mammals; Safety; Sodium Chloride; salt; Survival Rate; Technology; Testing; Toxicology; Translations; translation; United States Food and Drug Administration; Food and Drug Administration; USFDA; Universities; Virginia; Work; gemcitabine; Difluorodeoxycytidine; dFdC; dFdCyd; Drug Delivery; Drug Delivery Systems; Treatment outcome; Hygroscopicity; Wettability; Investigational New Drug Application; improved; Peripheral; Clinical; Penetration; Phase; Histologically; Histologic; Medical; Buccal Cavity; Buccal Cavity Head and Neck; Cavitas Oris; Mouth; Oral cavity; Malignant Tumor of the Lung; Pulmonary Cancer; Pulmonary malignant Neoplasm; lung cancer; Malignant neoplasm of lung; Oncology Cancer; Oncology; Toxicokinetics; Therapeutic; Deposition; Deposit; Intravenous; Route; Techniques; meter; Tumor Tissue; Operative Surgical Procedures; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; particle; Performance; novel; Bypass; Maximum Tolerated Dose; Maximal Tolerated Dose; Maximally Tolerated Dose; drug development; Effectiveness; Address; Dose; Tumor Burden; Tumor Load; Data; Dryness; Inhalation Toxicology; in vivo; Cancer Etiology; Cancer Cause; Cancer Patient; Rodent Model; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Characteristics; Pathway interactions; pathway; pre-clinical; preclinical; preclinical study; pre-clinical study; National Heart, Lung, and Blood Institute; NHLBI; Outcome; site targeted delivery; targeted delivery; scale up; innovate; innovative; innovation; chemotherapy; commercialization; tumor; standard of care; good laboratory practice; Formulation; systemic toxicity; efficacy study; Inhaling; Inhalation; first in man; first-in-human; side effect; translational potential; translational opportunities; Circulation; manufacture