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

使用术中肿瘤靶向可激活荧光显像剂改善肺癌手术

• 批准号: 10600351
• 负责人: Eric Scott Bensen
• 金额: $ 112.43万
• 依托单位: VERGENT BIOSCIENCE, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-08 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10600351
• 关键词: Acute; Address; Australia; Binding; Biological Sciences; Blood; Brain; Breast; Cancer Etiology; Cancer Patient; Cancerous; Caring; Cathepsins; Cause of Death; Cessation of life; Chronic; Clinic; Clinical; Clinical Trials; Collaborations; Colorectal; Colorectal Cancer; Diagnosis; Disease; Dose; Double-Blind Method; Drug Kinetics; Enrollment; Ensure; Equipment; Event; Excision; Family; Formulation; Freeze Drying; Goals; Head and neck structure; Histologic; Histopathology; Human Volunteers; Image; Image-Guided Surgery; Intravenous; Iowa; Label; Left; Lesion; Light; Location; Lung; Lung Neoplasms; Lung nodule; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Measures; Modality; Molecular Target; Near-infrared optical imaging; Nodule; Operating Rooms; Operative Surgical Procedures; Ovarian; Palpation; Patient Care; Patient Schedules; Patient-Focused Outcomes; Patients; Pennsylvania; Peptide Hydrolases; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; Phase II Clinical Trials; Placebo Control; Postoperative Period; Predictive Value; Process; Prognosis; Radiation therapy; Randomized; Recovery; Recurrence; Recurrent tumor; Respiratory Insufficiency; Risk; Safety; Site; Solid Neoplasm; Specific qualifier value; Specificity; Specimen; Stomach; Surgeon; Surgical Oncology; Survival Rate; Tactile; Techniques; Testing; Time; Tissues; Training; Translating; Tumor Tissue; United States; Universities; University Hospitals; Vial device; Visual; Visualization; arm; cancer diagnosis; cancer surgery; cancer type; carboxypeptidase C; clinically significant; curative treatments; falls; fluorescence imaging; high risk; imaging agent; imaging system; improved; malignant breast neoplasm; medical schools; molecular imaging; novel; open label; optical imaging; overexpression; phase 3 study; phase I trial; phase II trial; preclinical safety; standard of care; surgery outcome; surgical risk; tumor

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.

项目摘要/摘要 今年，美国有228,000多人将接受肺癌的诊断。只有14％-49％ 诊断后至少5年生存，生存率低于5％ 患有晚期IIIB或IV的患者。切除后肿瘤复发是关键因素 糟糕的预后。如果在手术期间留下任何癌组织，则侵袭性肿瘤的风险 复发急剧增加。这些复发性肿瘤迅速传播并对患者产生负面影响 临床前景。因此，在手术切除过程中准确识别肿瘤组织至关重要。尽管如此 需要，将术前图像转化为实时的手术套件，精确可视化仍然是一个 挑战;在肺癌的术中环境中，组织通常会移动，肺部被放气，并且 血液会掩盖手术领域。 Vergent Bioscience，Inc。开发了分子成像剂VGT-309， 满足这种迫切需要改善肿瘤术中可视化的需求。该代理被用作 手术前单次静脉注射剂量，之后它将与取消的更新的组织蛋白酶结合 组织，被激活和荧光。然后，可商购的近红外（NIR）成像系统可以 在手术期间使用以照亮肿瘤并使外科医生精确识别和去除肿瘤 边缘，确保没有取消的纸巾被留下。 VGT-309有一个宽阔的剂量成像窗口，可以 在不需要额外的培训或设备的情况下，将无缝集成到现有的手术工作流中。 广泛的临床前安全性，效率和剂量研究已验证VGT-309的使用来促进 各种实体瘤类型的切除。 1阶段1随机，双盲，安慰剂对照，单个 在2021年初完成了健康受试者的上升剂量研究，以评估安全性，耐受性和 VGT-309的药代动力学。在此试验期间，所有四剂均安全且耐受性良好，因此起始剂量 选择0.05mg/kg的肺癌患者目前正在进行2期临床 在澳大利亚确定最佳VGT-309剂量和时机的试验。在当前直接到II期 应用，vergent将1）生产VGT-309当前良好制造后的VGT-309药品 实践，以及2）与宾夕法尼亚大学医院合作，以评估该代理 第2阶段的开放标签研究，以评估35名患者的安全性，耐受性和效率 可疑或经过证明的肺癌的护理手术切除标准。一旦在我们的 第2阶段临床试验，VGT-309将在较大的多站点2B和3阶段研究中进行评估。最终， 我们计划将这种荧光，可活化的分子成像剂的使用扩展到其他实体瘤 作为结直肠，头部和颈部，卵巢，脑，胃和乳房。该代理有可能改变 手术肿瘤空间并优化接受肿瘤切除的患者的临床结果。