Bintrafusp Alfa: A Bifunctional Fusion Protein Targeting PD-L1 and TGF-beta, in Patients with Pretreated Colorectal Cancer: Results from a Phase I Trial

A phase I study of bintrafusp alfa showed early signs of clinical efficacy and a manageable safety profile in patients with heavily pretreated solid tumors. Colorectal cancer (CRC) is a heterogeneous and complex disease with limited treatment options. Targeting transforming growth factor beta (TGF-beta) and programmed death ligand 1 pathways may enhance antitumor efficacy. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-beta receptor II (a TGF-beta "trap") fused to a human IgG1 monoclonal antibody blocking programmed cell death ligand 1. We report results from an expansion cohort of a phase I study (NCT02517398) in patients with heavily pretreated advanced CRC treated with bintrafusp alfa. As of May 15, 2020, 32 patients with advanced CRC had received bintrafusp alfa for a median duration of 7.1 weeks. The objective response rate was 3.1% and the disease control rate was 6.3% (1 partial response, 1 stable disease); 2 patients were not evaluable. The safety profile was consistent with previously reported data.