Drug intelligence / Profile preview

bintrafusp alfa + cisplatin + gemcitabine

Development stage
Phase 2
Lead developer
Merck KGaA
Modality
Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous
01

Overview

Bintrafusp alfa + cisplatin + gemcitabine is an investigational combination therapy for cancer, specifically studied in first-line treatment of biliary tract cancer. Bintrafusp alfa is a bifunctional fusion protein consisting of the extracellular domain of TGF-β receptor II (acting as a TGF-β "trap") fused to a human IgG1 antibody that blocks programmed death ligand 1 (PD-L1). Cisplatin and gemcitabine are conventional chemotherapeutic agents: cisplatin is a platinum-based DNA crosslinking agent that induces apoptosis, and gemcitabine is a nucleoside analog that inhibits DNA synthesis. Bintrafusp alfa is designed to inhibit two key immunosuppressive and pro-tumorigenic pathways: TGF-β signaling and PD-L1-mediated checkpoint inhibition, thereby enhancing antitumor immune response and reducing tumor microenvironment-mediated resistance. The combination aims to provide synergistic antineoplastic effects by integrating immunotherapy with cytotoxic chemotherapy[1][2][3][4].

02

Targets

DNACD274 (Programmed cell death protein 1 ligand 1)RNR (Ribonucleotide reductase)TGFB1 (Transforming growth factor Beta-1 proprotein)TGFB2 (Transforming growth factor beta 2)TGFB3 (Transforming growth factor beta 3)TGFBR2 (TGF-β receptor type 2)

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