Background: Ipi/Nivo is now FDA approved for the first line treatment of patients (pts) with intermediate and poor risk mRCC but activity in IO refractory mRCC patients is still not well reported. Here we seek to report activity of Ipi/Nivo in IO refractory mRCC pts. Methods: In this retrospective review, we identified a total of 30 pts with mRCC from 4 academic medical centers across the USA who received salvage Ipi/Nivo after disease progression on IO therapy. Pts with only predominant clear cell histology were captured. Ipi/Nivo was administered as per CHECKMATE 214. Investigator-assessed response rate were noted. Immune related adverse events (irAE) were captured in accordance with CTCAE v5.0. Results: The baseline demographics included median age of 60 years (21-82), ECOG PS 0-2, and 73% (22) male and 27% (8) female. IMDC risk categories at the time of salvage Ipi/Nivo initiation were 23% (7), 60% (18) and 3% (1) with favorable, intermediate and poor risk, respectively. The median number of prior systemic therapies was 3 (1-6). Prior IO therapies included nivolumab monotherapy (14), avelumab plus axitinib (3), high dose interleukin-2 (3), pembrolizumab monotherapy (2) and Ipi/Nivo, nivolumab plus hypoxia inducible factor (HIF) inhibitor, atezolizumab plus interferon, atezolizumab monotherapy, pembrolizumab plus bevacizumab, pembrolizumab plus axitinib, varlilumab plus atezolizumab and an oral adenosine inhibitor (1 each). The median time on prior IO therapy was 7 months (1-50), best response was 3% (1) CR, 40% (12) PR, 23% (7) SD and 33% (10) PD. 73% (22) had restaging scans to assess response to ipi/nivo of which 17% (5), 3% (3) and 47% (14) showed PR, SD and, PD respectively. 37% (11) developed any grade irAEs and 6% (2) had grade ≥3 irAE including one patient with splenic rupture and one with rash and pneumonitis. Conclusions: Ipi/Nivo is feasible and safe in IO-refractory mRCC population with preliminary evidence of anti-tumor activity. Updated response data will be presented.