capmatinib + gefitinib

Capmatinib + gefitinib is a combination therapy targeting two distinct pathways in non-small cell lung cancer (NSCLC). This combination specifically addresses EGFR-mutated, MET-dysregulated NSCLC that has developed resistance to EGFR tyrosine kinase inhibitor (TKI) treatment. Capmatinib is a potent and selective MET inhibitor that targets the c-Met receptor tyrosine kinase. It inhibits the phosphorylation of both wild-type and mutant variants of c-Met triggered by hepatocyte growth factor binding, preventing downstream signaling and tumor cell proliferation. Gefitinib is an EGFR tyrosine kinase inhibitor that binds to the ATP-binding site of the enzyme. It blocks the downstream signaling cascades that would otherwise lead to increased cancer cell survival and uncontrolled proliferation. The combination has shown promising clinical activity, particularly in patients with high MET-amplified tumors, with a phase II overall response rate (ORR) of 47% in patients with a MET gene copy number ≥ 6, compared to an ORR of 27% across all patients in the phase Ib/II study.