(UroToday.com) Sunitinib has been the standard first-line treatment for metastatic clear cell RCC since 2007. However, nivolumab plus ipilimumab combination therapy has been recently approved in upfront treatment of metastatic clear cell RCC patients with IMDC intermediate/poor risk groups based on data in the CheckMate-214 trial.1 In this trial, the objective response rate (ORR) was 42% for nivolumab plus ipilimumab versus 27% for sunitinib; the median PFS was 11.6 months for nivolumab plus ipilimumab, compared to 8.4 months for sunitinib. In unselected metastatic clear cell RCC patients, frontline nivolumab provided a 28.7% objective response rate and a median PFS of 5.54 months.2 Analysis of transcriptomic data from frozen clear cell RCC tumors revealed four groups of patients (ccrcc1-4) with immune and angiogenic high/low features which could allow to better identify responders to either nivolumab, nivolumab plus ipilimumab or TKI. ccrcc1 “immune-low” and ccrcc4 “immune-high” tumors have been associated with the poorest outcomes, whereas ccrcc2 “angio-high” and ccrcc3 “normal-like” tumors have been associated with the best outcomes. The hypothesis for this study was that nivolumab should provide good outcomes for ccrcc4, nivolumab plus ipilimumab should be necessary to improve outcomes in ccrcc1, and TKIs (sunitinib or pazopanib) should provide good outcomes for ccrcc2 and ccrcc3. At the kidney cancer session at the virtual ESMO 2020 annual meeting, Dr. Yann Vano and colleagues provided the final results of the BIONIKK trial.