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BN-Brachyury + ado-trastuzumab emtansine + bintrafusp alfa + entinostat
- Development stage
- Unknown
- Lead developer
- Bavarian Nordic
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Vaccines & Immunotherapeutics, Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Small Molecules
- Administration
- Subcutaneous (BN‐Brachyury), Intravenous (ado‐trastuzumab Emtansine), Intravenous (bintrafusp Alfa), Oral (entinostat)
01
Overview
This is an investigational combination therapy comprising four agents, each with distinct mechanisms targeting cancer. **BN-Brachyury** is a therapeutic cancer vaccine designed to induce a T-cell immune response against the transcription factor brachyury, which is overexpressed in several solid tumors and associated with treatment resistance and metastasis[1][2][8]. **Ado-trastuzumab emtansine** is an antibody-drug conjugate consisting of trastuzumab linked to the cytotoxic agent DM1; it targets HER2-positive tumor cells, delivering the cytotoxin directly after binding HER2[6][9]. **Bintrafusp alfa** is a bifunctional fusion protein that simultaneously blocks PD-L1 and sequesters TGF-beta, aiming to both enhance anti-tumor immunity and inhibit pro-tumorigenic signaling[7][10]. **Entinostat** is an oral small molecule inhibitor of class I histone deacetylases (HDACs), acting as an epigenetic modulator to alter gene expression in tumor cells. This combination aims for synergistic antitumor effects by engaging immune activation, targeted cytotoxicity, checkpoint inhibition/TGF-beta blockade, and epigenetic modulation.
- Brand names
- Kadcyla (ado-trastuzumab emtansine)
- Other names
- BN‐Brachyury vaccineMVA Brachyury TRICOM vaccine
02
Targets
T (Brachyury transcription factor)ERBB2 (Erb-b2 receptor tyrosine kinase 2)CD274 (Programmed cell death protein 1 ligand 1)TGFB (GARP–latent transforming growth factor beta 1 complex)HDAC8 (Histone Deacetylase 8)TUBB (Tubulin (alpha and beta subunits))
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