The first line treatment paradigm for advanced ccRCC has rapidly evolved with an expanding number of combination anti-angiogenic/PD1/L1 regimens including axitinib/pembrolizumab, axitinib/avelumab, cabozantinib/nivolumab and likely lenvatinib/pembrolizumab being added to the existing VEGFR TKI monotherapy and ICI combination regimens. The gene discussed is KDR; the disease is nonpapillary renal cell carcinoma.