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）是儿童骨骼最常见的主要原发性恶性肿瘤， 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头中，其中最常见的是 股骨，胫骨和肱骨。当前针对被诊断为人类患者的护理疗法 OSA包括多代理新辅助化疗（阿霉素 +顺铂+/- 方法传送）然后进行原发病变的手术切除并调整化学疗法， 治愈约60％至70％的患者1-3。但是，多达40％的新诊断患者 出现局部疾病最终向肺部发展转移，表明 许多患者在诊断或 在该期间4中开发它们。患有儿童的5年生存率 转移性OSA极低，徘徊在20％-30％左右，这种速度尚未提高 超过30年2。显然，新型疗法迫切需要，特别是能够的分子 抑制OSA转移的过程。药物正在发展免疫调节肽 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 癌症类型。胡椒的抗肿瘤活性已被证明是一种单一疗法和 在包括OSA在内的多个癌症模型中的其他免疫/化学疗法结合 转移模型。已经获得了毒Tox数据，并提出了进行临床的建议 犬OSA患者的试验是人类和并发产品开发的翻译工具 用于兽医应用。额外的拟议工作正在启用1阶段人类 临床试验，包括GLP-TOX所需的制造药物和药品 和临床研究，GLP-TOX研究的完成和IND提交OSA 指示。