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**sorafenib + BIIB022** is an investigational drug combination consisting of sorafenib, a small molecule multikinase inhibitor, and BIIB022, a non-glycosylated human IgG4 monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R). Sorafenib inhibits several kinases involved in tumor cell proliferation and angiogenesis, notably RAF kinase, VEGF receptors, and PDGF receptor. BIIB022 binds IGF-1R via an allosteric mechanism, blocking signaling without Fc-mediated effector functions, and is believed to inhibit IGF-1R-driven survival and proliferation in cancer cells. The combination was tested in advanced hepatocellular carcinoma but was found not to be tolerable due to dose limiting toxicity at the lowest planned dose[3].
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