Drug intelligence / Profile preview

duligotuzumab + cobimetinib

Development stage
Unknown
Lead developer
Genentech
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

This drug is a combination of **duligotuzumab**, a humanized bispecific IgG1 monoclonal antibody that binds and inhibits both the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3/ERBB3), and **cobimetinib**, a selective small molecule inhibitor targeting mitogen-activated protein kinase kinase 1 and 2 (MEK1 and MEK2). Duligotuzumab blocks ligand (such as neuregulins) binding to EGFR and ERBB3, leading to internalization of ERBB3, inhibition of downstream HER dimer signaling, and potential antibody-dependent cell-mediated cytotoxicity. Cobimetinib reversibly inhibits MEK1/2, blocking signal transduction in the MAPK/ERK pathway, commonly hyperactivated in KRAS-mutant and BRAF-mutant tumors. The combination was evaluated in early-phase trials primarily for solid tumors with KRAS mutations, aiming for additive blockade of tumor proliferation and survival pathways, but its development was limited by toxicity and lack of efficacy[1][2][3][5][7].

Other names
duligotuzumab + cobimetinib
02

Targets

MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)ERBB3 (Erb-b2 receptor tyrosine kinase 3)EGFR T790M (Epidermal growth factor receptor T790M mutant)MEK2 (Dual specificity mitogen-activated protein kinase kinase 2)

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