Background: Tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. As combinations of vascular endothelial growth factor receptor tyrosine kinase inhibitiors (VEGFR-TKIs) and checkpoint inhibitors have proven to be toxic, alternatives with an improved AE profile are required. We present safety data from a phase Ib/II combination of tivozanib and nivolumab Methods: In this phase Ib/II study, tivozanib was administered orally at two dose levels, 1.0 mg and 1.5 mg, once daily for 21 days every 28 day cycle in combination with nivolumab 240 mg every 14 days intravenously. Results: Eighteen patients have been enrolled. Phase Ib is complete. Safety data is available for 13, 3 at 1.0 mg tivo; 10 at 1.5 mg tivo. The median age was 62; 11 patients were ECOG 0 and 5 ECOG 1; and there were 13 males. 16 had clear cell histology No patient in phase Ib experienced an DLT in cycle 1. Patients in phase II are receiving tivozanib at 1.5 mg. All patients experienced at least one AE. The most common adverse events were hypertension, asthenia, mucositis, diarrhea, hand foot syndrome, arthralgia, and pruritis. Five patients (38%) had grade 3-4 AEs. One patient had both elevated serum lipase and amylase and one patient had an SAE of symptomatic malignant hypertension complicated by a seizure. The other grade 3-4 AEs were pneumonitis, stomatitis, and elevated ALT. Conclusions: As expected from a VEGFR-TKI with high specificity and a preferable toxicity pattern as a single agent, the combination of tivozanib with nivolumab is safe and manageable at full dose of both drugs. Efficacy is pending. This data is based on limited exposure and should be interpreted with caution. Additional patients are being enrolled and treated. This begs the question if tivozanib could be added to a triple combination with ipilimumab and nivolumab. Clinical trial information: NCT03136627