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

Division Of Basic Sciences - Nci

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Abstract

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.