Clinical outcomes in metastatic renal cell carcinoma (mRCC) treated with combination of nivolumab and cabozantinib (nivo-cabo) in the salvage setting.

e16570 Background: The CheckMate 9ER trial showed that the combination of nivolumab and cabozantinib (nivo-cabo) in first line setting for treatment of mRCC was superior to sunitinib in terms of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and led to its FDA approval. We report outcomes of cohort of patients with mRCC treated with nivo-cabo in the salvage setting. Methods: We retrospectively reviewed 17 patients with mRCC treated at Winship Cancer Institute who progressed through at least one line of prior therapy. These patients were then treated with either sequences: [1] cabozantinib and then add nivolumab upon progression (n = 8) and [2] nivolumab/ipilimumab or nivolumab and then add cabozantinib upon progression (n = 9) with two with nivolumab and ipilimumab. Median PFS and OS rates, and clinical benefit (defined as complete response or partial response, or stable disease) were described. Results: Thirteen patients had clear cell histology and four patients had non-clear cell histology. For sequence [1], the mPFS for cabozantinib alone was 9.9 months and combination of nivolumab added to cabozantinib was 8.9 months. For sequence [2], the mPFS for nivolumab with or without ipilimumab was 5.9 months and combination of cabozantinib added to nivolumab was 10.4 months. The 12-month OS rate was 88% for sequence [1] and 89% for sequence [2]. The 24-month, OS rate was 50% for sequence [1] and 89% for sequence [2]. 5/8 (63%) patients in sequence [1] and 7/9 (78%) patients in sequence [2] had clinical benefit. 3/8 (37.5%) patients in sequence [1] and 2/9 (22%) patients in sequence [2] experienced immune-related adverse effects such as hypothyroidism (grade II for two patients), pneumonitis (grade II), hepatic transaminase elevations (grade II), and pancreatitis (grade III). No patients in sequence [1] needed dose reduction in cabozantinib once nivolumab was added. 3/9 (33%) patients had dose reduction in cabozantinib in sequence [2] due to diarrhea. Conclusions: Nivo-cabo demonstrates activity in the salvage setting but there is still need to understand the optimal sequencing of both agents in the treatment of mRCC. Outcomes from this combination treatment are to be further validated from ongoing phase III trial, PDIGREE (NCT03793166).