The role of circulating kidney injury molecule-1 (KIM-1) in metastatic renal cell carcinoma (mRCC): A biomarker analysis of Tide-A, a phase 2 study of first-line avelumab (ave) plus intermittent axitinib (axi).

• DOI: 10.1200/jco.2025.43.5_suppl.584
• Publication Date: 2025-02-18T14:33:57Z
• Authors: Chiara Ciccarese; Antonio Agostini; Martina Panebianco; Sebastiano Buti; Paolo Andrea Zucali; Davide Bimbatti; Emanuela Fantinel; Elena Verzoni; Caterina Accettura; Lucia Bonomi; Consuelo Buttigliero; Giuseppe Fornarini; Maria Giuseppa Vi...; Romina Rose Pedone; Geny Piro; Giulia Claire Giu...; Matteo Perrino; Giampaolo Tortora; Carmine Carbone; Roberto Iacovelli
• Keywords: Avelumab; Kidney cancer

584 Background: KIM-1 was evaluated as plasma circulating biomarker of microscopical residual disease, disease recurrence after nephrectomy, and potential benefit from adjuvant immunotherapy (IO). No data are available about its role in the metastatic setting. Tide-A is a phase 2 trial showing feasibility de-intensified strategy VEGFR-TKI interruption IO-maintenance mRCC pts treated with ave+axi. We investigated whether prognostic prospective cohort Tide-A. Methods: Treatment-naïve prior no symptomatic/bulky/liver received ave+axi, interrupted axi 36 weeks case response. performed proteomics analysis aptamer-based technology SomaScan 7K (Somalogic, USA) to characterize expression levels ≈7000 proteins. Levels aptamers (uniprot accession number Q96D42, aptamer ID:9021-1) were baseline samples normalized by Adaptive Normalization Maximum Likelihood (ANML) integrate correct for batch-effects. cut-off (10.456 relative fluorescence units [RFU]) determined Maximally Selected Rank Statistics using maxstat R package, Van der Waerden test log-rank scores methods. Outcomes high vs. low at analyzed overall population, adjusted IMDC groups duration ave-maintenance. Results: Of 79 enrolled Tide-A, 69 pts, which 9 (13%) KIM-1-high 60 (87%) KM-1-low. status significantly associated shorter OS (mOS 24.2 months [95%CI 21.1–NR] not reached (NR) KM-1-low; p=0.0019). The 2-yOS rate 90% KIM-1-low 56% (p=0.002). Significant correlation between retained when (table). significant observed progression-free survival (mPFS 22.9 29.9 low, respectively; p= 0.4). 29 that discontinued axi, 28 pts; median ave-maintenance 15.9 wks 25 NR 3 KIM-1-high, (p=0.19). Conclusions: High level an independent negative factor RCC VEGFR-TKI+IO combination, regardless IMDC. seems have key selection more likely TKI-intermittent strategy. Additional analyses ongoing identify predictive biomarkers improve tailored management pts. 2-year according Low P value Favourable 80% 95% 0.045 Int/Poor 25% 86% 0.006