Treating non-small cell lung tumors with a novel inhaled dry powder chemotherapeutic formulation

用新型吸入干粉化疗制剂治疗非小细胞肺肿瘤

基本信息

批准号：
10696996
负责人：
Bryce Beverlin II
金额：
$ 112.75万
依托单位：
QUENCH MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10696996
关键词：
Address Aerosols Blood Volume Bypass Cancer Etiology Cancer Patient Cells Characteristics Circulation Clinical Clinical Research Combination Drug Therapy Data Deposition Dose Drug Delivery Systems Dryness Effectiveness Electroencephalography Elements Equipment Contamination Excipients Formulation Growth Histologic Human Immunotherapy In Vitro Inhalation Inhalation Toxicology Inhalators Intravenous Investigational Drugs Investigational New Drug Application Lead Leucine Lung Lung Neoplasms Malignant neoplasm of lung Maximum Tolerated Dose Medical Medical Staff Medicine Metabolism Methods National Heart, Lung, and Blood Institute Nebulizer Non-Small-Cell Lung Carcinoma Oncology Operative Surgical Procedures Oral cavity Outcome Pathway interactions Patients Penetration Performance Peripheral Pharmaceutical Preparations Pharmacotherapy Pharyngeal structure Phase Powder dose form Production Research Risk Rodent Rodent Model Route Safety Small Business Innovation Research Grant Sodium Chloride Survival Rate Techniques Technology Testing Therapeutic Toxicokinetics Toxicology Translations Treatment outcome Tumor Burden Tumor Tissue United States Food and Drug Administration United States National Institutes of Health Universities Virginia Wettability Work chemotherapy commercialization drug development efficacy study first-in-human gemcitabine good laboratory practice improved in vivo innovation manufacture meter mortality novel particle pre-clinical preclinical study scale up side effect standard of care systemic toxicity targeted delivery translational potential tumor

项目摘要

Project Summary / Abstract 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. Project 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.

项目概要/摘要意义肺癌是癌症死亡的主要原因，其 5 年生存率低于 20% 标准护理治疗。问题尽管使用了积极的手术、联合化疗和免疫疗法，但治疗的一个主要限制是通过全身给药来控制原发性和转移性非小细胞肺肿瘤药物是由于血容量稀释和代谢而导致肺部药物浓度较低。有一个关键的未满足的医疗需求需要制定新策略来改善患者的治疗结果。创新与化疗的全身递送相反，吸入将化疗药物直接递送至肿瘤由于肺组织中局部药物浓度的增加，从而增强了其功效和安全性肺，降低循环中的全身药物水平，并降低全身毒性。差距使用雾化化疗药物的初步临床前体内研究已证明其疗效和确定了通过气雾剂输送的可行性，但有毒药物的雾化有重大缺点。这些缺点包括缺乏有效的外周气道渗透、口咽沉积高、污染设备的使用情况，以及对医务人员造成的附带气溶胶风险。项目目标为了解决这些缺点，我们正在开发一种通过化学疗法递送化疗药物的新方法吸入直接到达肺部肿瘤，以最大限度地提高气雾剂的有效性和安全性使用标准剂量的一小部分进行治疗。我们将创造一种新型干粉化疗制剂含有 FDA 批准的用于治疗非小细胞肺癌的化疗药物。目标该提案的目标是 1) 扩大领先的 Quench EEG 配方并进行表征、稳定性、和性能研究，2) 在已建立的吸入毒理学中进行支持 IND 的毒理学研究用于监管提交的啮齿动物模型。商业潜力将该技术转化为临床有益的吸入式化疗产品有可能通过提供有针对性的降低治疗效果，显着改善肺癌患者肺部肿瘤的治疗直接向肺部给药，同时最大限度地减少全身毒性。