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Pharmacology & human Phase 1 safety & dose escalation studies using anti-GP88 in aggressive breast cancer

药理

基本信息

批准号：
10252075
负责人：
Ginette Serrero
金额：
$ 82.69万
依托单位：
A AND G PHARMACEUTICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10252075
关键词：
Acute Address Animals Antineoplastic Agents Aromatase Inhibitors Biological Biological Markers Biological Response Modifier Therapy Blood Blood Tests Blood specimen Breast Cancer Model Breast Cancer Patient Breast Cancer Risk Factor Cell Line Cessation of life Chemistry Clinical Clinical Research Clinical Trials Comprehensive Cancer Center Data Deposition Diagnostic tests Disease Documentation Dose Drug resistance Enrollment Estrogen Antagonists Estrogen receptor positive Event Formulation Future Glycoproteins Growth Hormones Human Image Individual Injectable Institutional Review Boards Investigation Life Expectancy Link Liquid substance Malignant Neoplasms Mammary Gland Parenchyma Maryland Maximum Tolerated Dose Measurable Measures Monoclonal Antibodies Mus Nature Outcome PGRN gene Pathologic Patient Monitoring Patients Pharmaceutical Preparations Pharmacologic Substance Pharmacology Pharmacology Study Phase Play Population Population Decreases Process Production Radiation therapy Recombinants Recurrence Resistance Role Safety Schedule Serum Small Business Innovation Research Grant Solid Neoplasm Stable Disease Testing Therapeutic Tissue Banks Tissues Toxic effect Toxicology Tumor Tissue Universities Vial device Xenograft Model Xenograft procedure adverse event monitoring aggressive breast cancer autocrine base breast cancer diagnosis cancer cell chemotherapy cohort companion diagnostics cost cost effective design drug discovery first-in-human immunogenicity improved in vivo innovation intravenous injection malignant breast neoplasm neutralizing antibody new therapeutic target nonhuman primate novel strategies open label overexpression pre-clinical precision medicine preclinical development preclinical efficacy predictive marker real time monitoring response success targeted treatment theranostics therapeutic target therapy development treatment choice triple-negative invasive breast carcinoma tumor tumor growth tumorigenesis

项目摘要

In 2017, ~200,000 new cases of breast cancer (BC) and ~40,000 related deaths are expected in the US. ~30,000 of these are patients with aggressive triple negative BC (TNBC) or anti-estrogen/aromatase inhibitor resistant (AE/AI) BC that do not have targeted therapy and rely on radiotherapy and aggressive chemotherapy. A new approach that benefits these patients and provides increased life expectancy needs to be developed. We have identified GP88, a glycoprotein that is produced by cancer cells and stimulates their growth and survival leading to formation of more aggressive tumors. GP88 is found in BC but not in normal breast tissue. There is compelling biological and clinical evidence to suggest that GP88 can be used to develop novel targeted therapy with companion diagnostics that could impact treatment and improve survival of TNBC and AE/AI BC patients. We have developed a tissue test to identify patients with tumors expressing GP88 and an anti-GP88 (AG1) to block the action of GP88 on tumor tissues to a) inhibit tumor growth and b) increase the efficacy of current BC drugs. We have safety and efficacy data in animals and will in our Phase 1 develop a dosing strategy in mice before moving into human studies as part of the Phase 2. Additionally, a blood test has been developed to monitor patients while on treatment. Using AG1 as the therapy with two companion diagnostic tests, we will carry out a phase IA/B clinical trial in humans to determine safety of AG1 manufactured under GMP in the Phase 2 and will collect tumor tissue and blood on all patients to evaluate for GP88 expression (tissue) and concentration (blood).

2017年，预计美国将有约200，000例乳腺癌（BC）新发病例和约40，000例相关死亡。~30,000 其中包括侵袭性三阴性BC（TNBC）或抗雌激素/芳香化酶抑制剂耐药的患者 (AE/AI）没有靶向治疗，依赖放疗和积极化疗的BC。一个新需要开发一种使这些患者受益并延长预期寿命的方法。我们有发现了GP 88，一种由癌细胞产生的糖蛋白，刺激癌细胞的生长和存活，形成更具侵袭性的肿瘤GP 88在乳腺癌中有表达，但在正常乳腺组织中无表达。有令人信服生物学和临床证据表明，GP 88可用于开发新的靶向治疗，伴随诊断可能影响治疗并改善TNBC和AE/AI BC患者的生存率。我们已经开发了一种组织测试，以确定表达GP 88和抗GP 88（AG 1）的肿瘤患者， GP 88对肿瘤组织的作用是a）抑制肿瘤生长和B）增加目前BC药物的功效。我们有动物的安全性和有效性数据，并将在我们的第一阶段开发小鼠给药策略，作为第二阶段的一部分进入人体研究。此外，还开发了一种血液测试来监测患者在治疗期间。使用AG 1作为治疗与两个伴随诊断测试，我们将进行一项在人类中进行IA/B期临床试验，以确定在II期中根据GMP生产的AG 1的安全性，收集所有患者的肿瘤组织和血液以评估GP 88表达（组织）和浓度（血液）。