Drug intelligence / Profile preview

ado-trastuzumab emtansine + bintrafusp alfa + entinostat

Development stage
Unknown
Lead developer
Roche
Modality
Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Small Molecules
Administration
Intravenous, Oral
01

Overview

This is an investigational combination therapy consisting of three agents with distinct mechanisms of action, primarily under evaluation for cancer treatment: **Ado-trastuzumab emtansine** is an antibody-drug conjugate composed of the monoclonal antibody trastuzumab linked to the cytotoxic agent DM1. It targets HER2-positive cancer cells, delivering DM1 directly to these cells and inhibiting their proliferation. **Bintrafusp alfa** is a bifunctional fusion protein that simultaneously blocks programmed death-ligand 1 (PD-L1) and traps transforming growth factor-beta (TGF-beta), aiming to enhance anti-tumor immune responses by overcoming two major immunosuppressive pathways in the tumor microenvironment. **Entinostat** is a selective oral small-molecule inhibitor of class I histone deacetylases. By inhibiting HDACs, it induces hyperacetylation of histones, leading to transcriptional activation of genes involved in cell cycle arrest, differentiation, apoptosis, and modulation of immune responses[2][3][5]. The combination aims to synergistically target tumor cells through direct cytotoxicity, immune checkpoint inhibition/immune modulation, and epigenetic reprogramming.

Other names
T-DM1T-DM-1T-DM 1M7824M-7824M 7824SNDX 275SNDX275SNDX-275MS 275MS275MS-275
02

Targets

HDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)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)

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