Drug intelligence / Profile preview

afatinib + ramucirumab

Development stage: Preclinical
Lead developer: Boehringer Ingelheim
Modality: Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration: Oral, Intravenous

Overview

A combination therapy consisting of afatinib, a second-generation irreversible ErbB family inhibitor, and ramucirumab, a human IgG1 monoclonal antibody targeting VEGFR2. Afatinib covalently binds to and irreversibly blocks signaling from EGFR (ErbB1), HER2 (ErbB2), ErbB3, and HER4 (ErbB4), preventing tyrosine kinase autophosphorylation and downregulating ErbB signaling. Ramucirumab binds to the extracellular domain of VEGFR2, preventing binding of VEGF ligands and inhibiting angiogenesis. This combination has shown efficacy in treating EGFR-mutated non-small cell lung cancer (NSCLC), particularly in patients with uncommon mutations such as L861Q and G719X.

Targets

ERBB3 (Erb-b2 receptor tyrosine kinase 3)ERBB2 (Erb-b2 receptor tyrosine kinase 2)ERBB4 (Erb-b2 receptor tyrosine kinase 4)EGFR T790M (Epidermal growth factor receptor T790M mutant)VEGFR2 (Vascular endothelial growth factor receptor 2)

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