PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

Localized renal cell carcinoma (RCC) has an associated risk of recurrence after nephrectomy. Several clinical risk models attempt to predict oncologic outcomes based on clinical and pathologic features. In addition, novel gene signatures have been developed to refine risk prediction based on tumor biology. Systemic therapies targeting angiogenic pathways that are effective in metastatic RCC failed to show an improvement in overall survival in the adjuvant setting. Immune checkpoint inhibitors have shown significant antitumor activity with prolonged and durable responses in metastatic RCC, which led to an interest in evaluating these agents in the adjuvant setting. In this review, clinical risk-predictive models, novel gene signatures, major clinical trials completed in the adjuvant setting, ongoing immune checkpoint inhibitor trials, and the perspective of adjuvant treatment in RCC are discussed.

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669 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.