DEVELOPMENT OF NOVEL ANTICANCER AGENT TO POTENTIATE SENSITIVITY TO ANTI-ESTROGEN THERAPY

开发新型抗癌剂以增强抗雌激素治疗的敏感性

• 批准号: 8935272
• 负责人: GINETTE SERRERO
• 金额: $ 147.86万
• 依托单位: A AND G PHARMACEUTICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2016-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935272
• 关键词: Acute; Anti-Idiotypic Antibodies; Antineoplastic Agents; Biological; Cancer Patient; Cessation of life; Clinical; Clinical Research; Contracts; Data; Development; Development Plans; Disease; Dose; Drug Kinetics; Estrogen Antagonists; Estrogen Therapy; Estrogens; Human; Life; Malignant neoplasm of lung; Measures; Non-Small-Cell Lung Carcinoma; Nude Mice; Patients; Phase; Preparation; Production; Progranulin; Recombinant Antibody; Resistance; Safety; Solutions; Staging; Toxicology; Xenograft Model; Xenograft procedure; base; efficacy trial; improved; malignant breast neoplasm; manufacturing process; nonhuman primate; novel; pre-clinical; preclinical study; tumor growth

Our Phase I Contract demonstrated that AG1, an anti-GP88 (Progranulin) recombinant antibody potentiated the efficacy of anti-estrogen (AE) based therapy to inhibit tumor growth in breast cancer xenografts. Additionally we have demonstrated that AG1 is efficacious as a single agent in lung cancer xenografts. The significant: >50% of estrogen positive (ER+) breast cancer patients are, or become insensitive to AE therapy and ~50% lung cancer patients die even when disease is detected at an early stage. Thus potentiating efficacy of AE in ER+ breast cancer potentially offers a treatment solution for AE resistant patients and improving treatment options for early stage lung cancer may reduce the number of deaths. These biological data, together with the complete manufacturing process and stability studies that we have developed for AG1, supports moving AG1 into final pre-clinical studies. The PI is requesting support in form of a Phase II contract to enable the production of a batch of AG1, complete dosing studies, and perform repeat-dose in life toxicology (Acute dose previously performed), pharmacokinetics and dose assessment in non-human primates and file an IND with the US FDA for first in human safety and efficacy studies for indications of breast and lung cancer.

我们的I期合同证明，AG1（一种抗GP88（颗粒蛋白前体）重组抗体）增强了基于抗雌激素（AE）的治疗在乳腺癌异种移植物中抑制肿瘤生长的疗效。此外，我们已经证明AG1作为单一药物在肺癌异种移植物中是有效的。重要的是：>50%的雌激素阳性（ER+）乳腺癌患者对AE治疗不敏感或变得不敏感，约50%的肺癌患者即使在早期检测到疾病也会死亡。因此，增强AE在ER+乳腺癌中的疗效可能为AE耐药患者提供治疗解决方案，改善早期肺癌的治疗选择可能减少死亡人数。这些生物学数据以及我们为AG1开发的完整生产工艺和稳定性研究支持将AG1转入最终临床前研究。PI请求以II期合同的形式提供支持，以生产一批AG1，完成给药研究，并在非人灵长类动物中进行重复给药毒理学（先前进行的急性给药）、药代动力学和剂量评估，并向美国FDA提交IND，用于首次在乳腺癌和肺癌适应症的人体安全性和疗效研究。