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).

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