Phase II Trial of Bintrafusp Alfa in Subjects with Thymoma and Thymic Carcinoma

Bintrafusp Alfa 在胸腺瘤和胸腺癌受试者中的 II 期试验

• 批准号: 10487117
• 负责人: Arun Rajan
• 金额: $ 20.2万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487117
• 关键词: Aftercare; Biological Markers; Biology; Cells; Chimeric Proteins; Clinical; Disease; Dose; Enrollment; Epithelial; Evaluation; Immune; Institutional Review Boards; Malignant neoplasm of thymus; Non-Small-Cell Lung Carcinoma; PDL1 inhibitors; Patients; Phase I Clinical Trials; Progression-Free Survivals; Protocols documentation; Recurrence; Refractory; Relapse; Safety; Solid Neoplasm; Thymic Carcinoma; Thymoma; Thymus Gland; Tissues; Transforming Growth Factors; United States National Institutes of Health; anti-PD-1/PD-L1; base; burden of illness; chemotherapy; cohort; design; experience; immune-related adverse events; medication safety; objective response rate; patient population; phase 2 study; phase II trial; programmed cell death ligand 1; response; tumor

Bintrafusp alfa, a bifunctional fusion protein that targets PD-L1 and transforming growth factor-b (TGF-b) has shown activity against heavily pre-treated solid tumors including non-small cell lung cancer previously treated with single-agent anti-PD-1/PD-L1 inhibitors (please refer to the biomarker cohort of protocol 15-C-0179, which is listed among my ongoing projects). Retrospective analysis of pre-chemotherapy tissue obtained from 20 patients with stage IV thymic carcinoma and 13 cases of stage III/IV thymoma, showed TGF-b expression in 65% cases of thymic carcinoma and 15% cases of thymoma with a lower median survival among patients with thymic carcinoma (30 months versus 63 months). As part of the dose escalation cohort of an NCI phase I clinical trial (15-C-0179), treatment with bintrafusp alfa resulted in a brief period of disease stabilization and no immune-related adverse events in one patient with heavily pre-treated, WHO subtype B3 thymoma with a large disease burden. Based on our experience with bintrafusp alfa and evaluation of TGF-b biology in recurrent thymic cancers, we will evaluate bintrafusp alfa in patients with recurrent TETs to define the clinical activity and safety of the drug in this patient population. A phase II study has been designed and approved by the NIH IRB (protocol 20-C-0097) and is expected to start enrollment in August 2020.

Bintrafusp alfa, a bifunctional fusion protein that targets PD-L1 and transforming growth factor-b (TGF-b) has shown activity against heavily pre-treated solid tumors including non-small cell lung cancer previously treated with single-agent anti-PD-1/PD-L1 inhibitors (please refer to the biomarker cohort of protocol 15-C-0179, which is listed among my ongoing projects).回顾性分析从20例IV期胸腺癌和13例III/IV期胸腺瘤患者获得的化学疗法组织，在65％的胸腺癌和15％的胸腺瘤病例中表现出TGF-B表达，胸腺瘤患者中位数较低的胸腺瘤生存期（30个月（30个月）为63个月）。作为NCI I期临床试验（15-C-0179）剂量升级队列的一部分，用Bintrafusp ALFA治疗导致疾病的短暂疾病稳定，并且在一名患有大量预处理的患者中没有免疫相关的不良事件，该患者是B3胸腺瘤和较大的疾病繁殖力。根据我们对复发性胸腺癌中TGF-B生物学的评估的经验，我们将评估复发TET患者的Bintrafusp alfa，以定义该患者人群中药物的临床活性和安全性。 NIH IRB（协议20-C-0097）设计和批准了II期研究，预计将于2020年8月开始入学。