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

2017年，美国预计将新增约20万例乳腺癌(BC)病例和约4万例相关死亡。~30,000 其中有侵袭性三阴性BC(TNBC)或抗雌激素/芳香酶抑制剂耐药的患者 (AE/AI)BC，没有靶向治疗，依靠放射治疗和积极的化疗。一种新的 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 确定了GP88，一种由癌细胞产生并刺激其生长和存活的糖蛋白 形成更具侵袭性的肿瘤。在BC中发现了GP88，但在正常乳腺组织中没有发现。有令人信服的 生物学和临床证据表明，GP88可用于开发新的靶向治疗 伴随诊断，可影响治疗并提高TNBC和AE/AI BC患者的存活率。我们 我开发了一种组织测试来识别表达GP88和抗GP88(AG1)的肿瘤患者 GP88对肿瘤组织的作用是：a)抑制肿瘤生长；b)提高现有BC药物的疗效。 我们已经有了动物的安全性和有效性数据，并将在我们的第一阶段开发一种在小鼠身上的给药策略 作为第二阶段的一部分进入人体研究。此外，已经开发了一种血液测试来监测 患者在治疗过程中。使用AG1作为治疗方法，并进行两项伴随的诊断试验，我们将进行一项 人体IA/B期临床试验，以确定在GMP下生产的AG1在第二阶段的安全性，并将 收集所有患者的肿瘤组织和血液，以评估GP88的表达(组织)和浓度(血液)。

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).