Background: The therapeutic armamentarium in mRCC underwent a rapid change during the recent past. LenEve, proved to be effective as subsequent treatment in mRCC in clinical trials.Here, we evaluate efficacy and safety in mRCC patients in a real-world setting. Methods: mRCC patients who started LenEve treatment between 08/2016 and 12/2021 at 6 tertiary German centers were retrospectively analyzed. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR), were evaluated per local investigator. Subgroup analyses by risk scores, previous therapies and initial dosing were performed. Results: Eighty-one patients were assessed: Median age was 61 years (range 42-80), 81.5% were males, ECOG score was 0 to 1 in 80.2%. Synchronous metastases were found in 39.5% of patients. The median number of treatment lines prior to LenEve was 3. Median treatment duration with LenEve was 6.1 months (range 0.2-29.2). The ORR, DCR, median OS and PFS was 28.4%, 61.7%, 11.3 months (95% CI 8.7-13.9) and 6.5 months (95% CI 5.4-7.6), respectively. Across patients with 0-2 compared to ≥3 previous therapeutic lines median PFS, OS and ORR were similar, as well as for patients with or without previous immunotherapy. Safety was manageable, with 6.2% of patients discontinuing treatment due to treatment related adverse events. Conclusions: High efficacy in second- and later-line in a heavily pre-treated real-world cohort of mRCC patients was demonstrated by LenEve, regardless of treatment line, IMDC risk group, initial dosing or previous treatment with immunotherapy.