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durvalumab + dabrafenib + trametinib

Development stage
Preclinical
Lead developer
AstraZeneca
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous (durvalumab), Oral (dabrafenib, Trametinib)
01

Overview

**durvalumab + dabrafenib + trametinib** is a triple combination investigational therapy composed of **durvalumab** (a monoclonal antibody against PD-L1), **dabrafenib** (a small molecule BRAF inhibitor), and **trametinib** (a small molecule MEK inhibitor). - **Durvalumab** binding to PD-L1 blocks its interaction with PD-1 and CD80, thereby restoring T-cell activity and promoting anti-tumor immune responses[5]. - **Dabrafenib** inhibits the BRAF V600-mutant kinase, suppressing abnormal MAPK pathway signaling and restricting tumor cell growth[1][2][3][7][9]. - **Trametinib** inhibits MEK1 and MEK2, downstream components of the MAPK pathway, complementing BRAF inhibition and limiting resistance mechanisms[1][2][3][7][9]. Combining **immune checkpoint inhibition** (durvalumab) with **targeted BRAF and MEK blockade** (dabrafenib and trametinib) aims to potentiate tumor immunogenicity and overcome resistance, under investigation primarily in advanced and metastatic solid tumors (especially melanoma and colorectal cancer)[5]. Durvalumab was developed by AstraZeneca. Dabrafenib and trametinib were initially developed by GlaxoSmithKline, now manufactured by Novartis.

Other names
anti-PD-L1 antibody (durvalumab)BRAF inhibitor (dabrafenib)MEK inhibitor (trametinib)
02

Targets

BRAF (B-Raf proto-oncogene, serine/threonine kinase)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)CD274 (Programmed cell death protein 1 ligand 1)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)

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