ningetinib + gefitinib

**Ningetinib + gefitinib** is a combination therapy of two small molecule tyrosine kinase inhibitors for the treatment of non-small cell lung cancer (NSCLC), especially in patients with acquired resistance to EGFR-TKIs and negative for T790M mutation. Ningetinib inhibits c-Met, AXL, VEGFR-2, Mer, and Flt3 kinases, while gefitinib inhibits the epidermal growth factor receptor (EGFR). The combination is designed to overcome resistance mechanisms involving MET and AXL dysregulation by simultaneously blocking MET/AXL and EGFR signaling. Ningetinib acts by inhibiting MET/AXL/VEGFR-2 pathways, and gefitinib blocks EGFR-driven proliferation. Both have interaction with drug-metabolizing enzymes (e.g., CYP1A1) and drug transporters (P-gp, BCRP). Combination treatment has shown clinical activity and tolerability in clinical trials, with notable efficacy in EGFR-mutant NSCLC harboring MET or AXL dysregulations[1][2][3].