Development of an immunomodulating peptide as a therapy for osteosarcoma in canine and human

开发免疫调节肽作为犬和人类骨肉瘤的治疗方法

• 批准号: 10822577
• 负责人: Joshua Alfaro
• 金额: $ 99.51万
• 依托单位: PHARMAIN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10822577
• 关键词: Accounting; Acute; Adjuvant Chemotherapy; Adolescent; Biological Assay; C-Type Natriuretic Peptide; Cancer Model; Canis familiaris; Chest; Child; Cisplatin; Clinical; Clinical Research; Clinical Trials; Cyclic GMP; Data; Data Set; Development; Diagnosis; Disease; Dose; Doxorubicin; Engineering; Excision; Feedback; Femur; Formulation; Freeze Drying; Freezing; Funding; Human; In Vitro; Lead; Life; Liquid substance; Localized Disease; Lung; Malignant Neoplasms; Measures; Metastatic Neoplasm to the Lung; Metastatic Osteosarcoma; Methods; Methotrexate; Micrometastasis; Modeling; Neoadjuvant Therapy; Neoplasm Metastasis; Newly Diagnosed; Operative Surgical Procedures; Patients; Pediatric Neoplasm; Peptides; Perioperative; Pharmaceutical Preparations; Phase; Population Control; Primary Lesion; Process; Progressive Disease; Property; Rattus; Reporting; Sampling; Small Business Innovation Research Grant; Specific qualifier value; Survival Rate; Time; Translations; Work; analytical method; antifibrotic treatment; bone; cancer type; chemotherapy; humerus; immunoregulation; improved; limb bone; long bone; manufacture; meetings; novel therapeutics; osteosarcoma; product development; standard of care; success; tibia; tool; tumor

Osteosarcoma (OSA) is the most common primary malignancy of bone in children and adolescents, accounting for approximately 5% of all childhood tumors (www.cancer.gov). Osteosarcoma occurs primarily in the long bones of the limbs, including most commonly the femur, tibia, and humerus1. The current standard of care therapy for human patients diagnosed with OSA includes multi-agent neoadjuvant chemotherapy (doxorubicin + cisplatin +/- methotrexate) followed by surgical resection of the primary lesion and adjuvant chemotherapy, curing approximately 60 to 70% of patients 1–3. However, up to 40% of newly diagnosed patients presenting with localized disease eventually develop metastases to the lung, indicating that many patients already have micrometastases present in the lung at the time of diagnosis or develop them during the perioperative period 4. The 5-year survival rate for children with metastatic OSA is extremely low, hovering around 20%-30%, a rate that has not improved in over 30 years 2. Clearly, novel therapies are in critical need, specifically molecules capable of inhibiting the process of OSA metastasis. PharmaIN is developing immunomodulating peptide with unique anti-tumor and anti-fibrotic properties for the treatment of osteosarcoma and other cancer types. The peptide’s anti-tumor activity has been demonstrated as a monotherapy and combination with other immuno/chemotherapies in multiple cancer models, including OSA metastatic model. Pilot tox data has been obtained and PharmaIN proposes to conduct a clinical trial in canine OSA patients as a translation tool for human and concurrent product development for veterinary applications. The additional proposed work is IND enabling for a Phase 1 human clinical trial and consists of manufacturing drug substance and drug product needed for GLP-tox and clinical studies, completion of GLP-tox studies and submission of the IND for the OSA indication.

骨肉瘤（OSA）是儿童最常见的原发性骨恶性肿瘤， 青少年，约占所有儿童肿瘤的5%（www.cancer.gov）。 骨肉瘤主要发生在四肢的长骨中，最常见的包括 股骨、胫骨和肱骨1。目前诊断为人类患者的护理治疗标准 包括多药新辅助化疗（阿霉素+顺铂+/-顺铂）， 甲氨蝶呤），然后手术切除原发病灶和辅助化疗， 治愈约60 - 70%的患者1-3。然而，高达40%的新诊断患者 表现为局部疾病的患者最终会转移到肺部，这表明， 许多患者在诊断时已经在肺中存在微转移， 在围手术期开发它们4.儿童的5年生存率 转移性OSA的发生率极低，徘徊在20%-30%左右， 超过30年2。显然，新的治疗方法是迫切需要的，特别是能够 抑制OSA转移的过程。PharmaIN正在开发免疫调节肽 具有独特的抗肿瘤和抗纤维化特性，用于治疗骨肉瘤和其他疾病， 癌症类型。该肽的抗肿瘤活性已被证明是单一疗法， 在多种癌症模型（包括OSA）中与其他免疫/化疗联合 转移模型已获得中试毒理学数据，PharmaIN建议进行临床试验。 在犬OSA患者中进行的试验，作为人类和并行产品开发的翻译工具 用于兽医应用。额外的拟议工作是IND使1期人类 临床试验，包括生产GLP-tox所需的原料药和制剂 和临床研究，完成GLP-tox研究并提交OSA IND 适应症