Background: TIVO, a potent tyrosine kinase inhibitor that predominantly targets vascular endothelial growth factor receptors, is approved as a third or later line therapy for advanced RCC based on improved progression-free survival (PFS) compared with sorafenib in the TIVO-3 trial. However, TIVO-3 was conducted before immune checkpoint-based therapies (ICT), cabozantinib (CABO), and lenvatinib/everolimus (LEN/EVE) became fully incorporated in the sequential treatment paradigm for advanced ccRCC. Hence, an appraisal of the role of TIVO in the current RCC treatment landscape is warranted. Methods: We performed a retrospective study of pts with advanced ccRCC treated with TIVO at MD Anderson Cancer Center during 6/2021-7/2023. Demographic and clinical data were abstracted from the electronic medical records. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed objective response rate (ORR), clinical benefit rate [percentage of all treated pts who achieved a complete or partial response (PR) or had stable disease (SD) for ≥6 months (mo)], time on treatment (TOT), PFS, overall survival (OS), and safety. Results: 30 pts (23 males, 7 females; median age 66 years, range 43-80) were included in this analysis. Median follow-up was 10.8 mo. At initiation of TIVO, 77% of pts had ECOG PS 0/1, 23% had PS ≥2; 53% had intermediate-risk and 47% had poor-risk disease by IMDC; 83% had ≥3 metastatic sites; 80% had prior nephrectomy. Median number of prior therapies was 4 (range, 1-8). All pts received prior ICT (30% nivolumab/ipilimumab), 40% received prior axitinib, 87% CABO and 60% LEN +/- EVE. 23 pts (76.7%) started TIVO at full-dose (1.34 mg/day, 3 weeks on, 1 week off) and 7 pts (23.3%) at 0.89 mg/day, 3 weeks on, 1 week off. Of 26 pts with evaluable radiographic response, 2 pts had a confirmed PR (ORR 7.7%) and 5 pts had SD for ≥6 mo (clinical benefit rate 23.3%). Median TOT was 3.2 mo (range, 0.1-13.5), median PFS 3.7 mo (range, 0.7-13.5); median OS has not been reached (13 pts had died at time of analysis). 7 pts (23.3%; 5 pts who started at 1.34 mg/d and 2 pts who started at 0.89 mg/d) required dose-reduction due to treatment related adverse events (TRAEs). 15 pts (50%) had ≥1 any grade TRAE; 4 pts (13.3%) had any grade hypertension. There were 6 Grade ≥3 TRAEs [congestive heart failure (3), hypertension, mucositis, GI perforation]. 5 pts (16.6%) were continuing treatment with TIVO at time of analysis; 20 pts (66.7%) discontinued TIVO due to progressive disease, 3 pts (10%) for TRAEs, and 2 pts for other reasons (infection, worsening of prior ICT-mediated neuropathy). 1 pt died of TIVO-related GI perforation. Conclusions: In this cohort of heavily pretreated pts with advanced ccRCC, TIVO yielded a modest clinical benefit in a minority of pts who received prior ICT, CABO, and LEN +/- EVE. TRAEs observed with TIVO were consistent with previously published reports.