Traditionally known to be chemotherapy-resistant, renal cell carcinoma (RCC) still poses a significant health care burden. It is currently the eighth leading cause of cancer mortality in the United States. The estimated overall survival of all stages is around 75%; however, less than 15% of patients with metastatic disease survive for 5 years.1 Very little progress was achieved between the 1992 approval of IL-2, a toxic treatment with modest activity at best, and the approval of the first anti-angiogenic agent in 2006. Nevertheless, the trudge seems to have picked up the pace since the introduction of immune checkpoint inhibitors (ICIs), which emerged as an essential component of frontline therapy in patients with intermediate to high-risk disease. Furthermore, ICIs combinations demonstrated superior outcomes to single-agent anti-angiogenic. For instance, the combination of either pembrolizumab and axitinib, or nivolumab and cabozantinib, in untreated metastatic RCC produced a significant improvement in overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) compared to single-agent sunitinib in the intermediate and poor-risk groups.2-4 In addition, the combination of two ICIs, nivolumab, and ipilimumab, also produced superior outcomes to single-agent sunitinib in the CheckMate 214 trial in the first-line setting.5,6