Based on these preclinical and early clinical data, we conducted a phase II study to evaluate the efficacy and safety of single-agent sapanisertib and sapanisertib in combination with TAK-117 compared with everolimus in patients with advanced or metastatic ccRCC that had progressed on or after VEGF-targeted therapy; thus testing the hypothesis that dual mTORC1/2 inhibition, either with or without additional PI3Kα inhibition, will provide better efficacy than single-agent rapalog inhibition of mTORC1. Here, VEGFA is linked to nonpapillary renal cell carcinoma.