cabozantinib + panitumumab

Cabozantinib + panitumumab is an investigational combination therapy for metastatic colorectal cancer, particularly in patients with RAS wild-type or MET-amplified tumors who have progressed on standard therapies. Cabozantinib is a small molecule multi-kinase inhibitor that targets several receptor tyrosine kinases, including c-MET, VEGFR2, AXL, RET, ROS1, KIT, TIE2 and others. Panitumumab is a fully human IgG2 monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), blocking ligand binding and downstream signaling. The rationale for combining these agents is to overcome resistance to anti-EGFR therapy mediated by MET amplification; cabozantinib inhibits MET-driven pathways while panitumumab blocks EGFR signaling. Clinical studies have shown some antitumor activity but also notable toxicity requiring dose reductions[1][2][5][8].