JMT101 + afatinib

JMT101 + afatinib is a pharmaceutical drug combination under investigation for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations and advanced esophageal squamous cell carcinoma. JMT101 is an anti-EGFR IgG1 monoclonal antibody with a backbone derived from cetuximab but engineered for reduced immunogenicity and increased affinity for EGFR compared to cetuximab. Afatinib is a small molecule, irreversible tyrosine kinase inhibitor (TKI) that covalently blocks the kinase domains of EGFR and other members of the ErbB family (HER2, ErbB3, ErbB4). Mechanistically, JMT101 binds to the extracellular domain of EGFR, facilitating receptor internalization and downregulation via Fc-dependent cytotoxicity, while afatinib inhibits phosphorylation and downstream EGFR signaling. The combination provides a more thorough and sustained EGFR blockade, overcoming resistance associated with EGFR exon 20 insertions, which are usually refractory to TKIs alone.

Other names

JMT101JMT-101JMT 101afatinibBIBW 2992BIBW2992BIBW-2992