binimetinib + crizotinib

Binimetinib + crizotinib is an investigational oral combination therapy consisting of two small molecule kinase inhibitors. Binimetinib is a selective inhibitor of MEK1 and MEK2 (mitogen-activated protein kinase kinases 1 and 2), which are key components in the RAS/RAF/MEK/ERK signaling pathway. Crizotinib is a multi-targeted tyrosine kinase inhibitor that primarily inhibits MET (hepatocyte growth factor receptor), ALK (anaplastic lymphoma kinase), and ROS1 kinases. The rationale for combining these agents stems from preclinical evidence that MET/STAT3 signaling mediates resistance to KRAS-MEK inhibition in RAS-mutant cancers; thus, dual blockade may overcome feedback mechanisms driving tumor progression. This combination has been studied primarily in advanced solid tumors with RAS mutations—most notably metastatic colorectal cancer (CRC)—to assess safety and preliminary efficacy[1]. In clinical studies, the regimen demonstrated pharmacodynamic target engagement but was limited by poor tolerability and did not yield objective responses in RAS-mutant CRC patients[1].