amivantamab + capmatinib

Amivantamab + capmatinib is an investigational combination therapy for advanced or metastatic non-small cell lung cancer (NSCLC) with MET alterations, including MET exon 14 skipping mutations and MET amplification. Amivantamab is a fully human bispecific monoclonal antibody that targets both the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET), blocking their extracellular domains and directing immune cell activity against tumor cells. Capmatinib is a small molecule tyrosine kinase inhibitor that selectively inhibits the intracellular kinase activity of the c-Met receptor, thereby blocking downstream signaling pathways involved in tumor proliferation and survival. The rationale for combining these agents is to achieve more potent inhibition of MET-driven oncogenic signaling by targeting both extracellular and intracellular domains simultaneously[1][5][8]. This combination is being evaluated in clinical trials for patients with advanced NSCLC lacking EGFR or ALK mutations who have progressed on or are intolerant to prior therapies[1][3][5].