Background: LEN+PEM is an approved first-line therapy for aRCC. In the CLEAR study, it produced a 71% objective response rate (ORR), an 18% complete response rate, and improved progression-free survival (PFS) and overall survival (OS) compared to sunitinib. CABO is approved as second and later line therapy for aRCC. We explored the efficacy of CABO in pts with aRCC after treatment with LEN+PEM. Methods: This is a retrospective study of pts with aRCC who received CABO after LEN+PEM at our institution from 12/2019 to 8/2023. Demographics and clinical data were abstracted from the EMR. A blinded radiologist assessed tumor response using RECIST v1.1. We measured PFS, time on therapy (TOT) and OS from start date of CABO. Results: 22 pts were analyzed (Table 1). Median follow up was 7.7 months (mo); 11 pts received LEN+PEM on the HOPE 111 trial (NCT02501096). Among all 22 pts, 11 (50%) had a partial response (PR), 5 (22.7%) had stable disease (SD), and 6 (27.3%) had progressive disease (PD) on LEN+PEM. Median TOT with LEN+PEM was 7.4 mo (range: 1.8-29). 20 pts (90.9%) discontinued LEN+PEM due to PD, 1 pt (4.5%) due to fatigue, and 1 pt (4.5%) due to elevated liver enzymes. 17 pts received CABO right after LEN+PEM; 3 pts received 1 line and 2 pts received 2 lines of therapy before CABO after LEN+PEM. Of 19 pts with evaluable radiographic response on CABO, 1 pt had a PR (ORR 5.3%, PFS 16.1 mo) and 3 pts had SD for ≥6 mo. Median TOT with CABO was 4.3 mo (range: 0.2-18.2); 13 pts (59.1%) took CABO for ≥4 mo, 7 pts (31.8%) took it for ≥6 mo, of which 3pts receivedpalliative radiation andcontinued CABO therapy beyond PD. Median PFS and median OS with CABO were 4.1 mo (range: 1.2-16.1) and 8.1 mo (range: 0.8-22.5), respectively. At time of analysis, 4 pts were still taking CABO (3 SD, 1 not yet evaluated); 15 pts discontinued CABO: 12 for PD, 1 for Grade 3 hand-foot skin reaction, 1 per pt request, and 1 for transition to hospice; 3 pts died during CABO therapy (bowel obstruction [1], COVID-19 [1], cardiac arrest [1]). Adverse events attributed to CABO were consistent with published reports. Conclusions: In this cohort of heavily pretreated pts who received CABO after LEN+PEM, CABO demonstrated a modest clinical benefit in a minority of pts, underscoring the need to develop effective novel therapies for aRCC.