KIM-1 as a circulating biomarker in metastatic RCC: Post-hoc analysis of JAVELIN Renal 101.
Authors: Machaalani Marc , Saliby Renee Maria , Zhong Caiwei , Saad Eddy , Steiner Clara , Liu Xiaowen , Cai Ti , Sun Maxine , Lee Gwo-Shu Mary , Xie Wanling , McDermott David F. , Choueiri Toni K. , Xu Wenxin 
Published: February 2025

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Background:
Kidney injury molecule-1 (KIM-1) is a circulating biomarker for renal cell carcinoma. The JAVELIN Renal 101 trial established avelumab and axitinib as a standard treatment regimen for advanced renal cell carcinoma (aRCC). In this post-hoc analysis, we evaluated whether baseline plasma KIM-1 and KIM-1 change on treatment are associated with outcomes in JAVELIN Renal 101.
Methods:
Patients with aRCC were randomized to avelumab plus axitinib (Av/Ax) or sunitinib (Sun), as previously described. KIM-1 was measured in plasma at baseline (C1D1) and at C3D1 using a Luminex microbead-based assay and an MSD electrochemiluminescence-based assay. KIM-1 values were categorized into high and low according to an optimized cutoff based on the maximum log-rank Q-statistic for PFS. Cox regression analyses were performed for OS and PFS and adjusted for baseline clinical characteristics. Associations between KIM-1 levels and clinical and transcriptomic data were evaluated using the Wilcoxon rank-sum test.
Results:
Plasma for analysis was available from 612 patients (69% of the ITT population), including 323 treated with Av/Ax and 289 with Sun. 57% of patients had high KIM-1 at baseline. In all patients, lower circulating KIM-1 at baseline was associated with longer progression-free survival (PFS) and overall survival (OS) (Table). Baseline KIM-1 levels were significantly lower in angiogenic (1-2) vs immune (4-5) transcriptomic clusters (p=0.002), responders vs non-responders (p=0.01), and exceptional vs intermediate responders (p=0.0015). In paired analyses, circulating KIM-1 decreased from baseline to C3D1 (p<0.0001) in both arms. Decrease in KIM-1 from baseline to C3D1 was associated with longer PFS and OS (Table). Luminex and MSD antibody-based assays had good concordance for distinguishing higher vs lower KIM-1 when measured in the same samples (Spearman’s ρ = 0.737), but absolute values of KIM-1 differed between the two assays (p<0.0001).
Conclusions:
This is the first study to evaluate circulating KIM-1 among patients with aRCC receiving immune checkpoint inhibitor and VEGF tyrosine kinase inhibitor combination therapy. Lower baseline plasma KIM-1 and decrease during treatment were associated with better prognosis. The distribution of circulating KIM-1 is assay-dependent and standardized cutoffs are needed before KIM-1 can be used in clinical decision making.

Association of baseline KIM-1 and KIM-1 change on treatment with outcomes.

Entire CohortHR (95% CI)
SunitinibHR (95% CI)
Avelumab + AxitinibHR (95% CI)

PFS(KIM-1 low vs high)
0.76 (0.58–0.99)
0.67 (0.47–0.95)
0.88 (0.61–1.28)

OS(KIM-1 low vs high)
0.58 (0.38–0.88)
0.46 (0.26–0.81)
0.79 (0.43–1.47)

PFS(KIM-1 decrease vs increase)
0.65 (0.46–0.87)
0.66 (0.46–0.96)
0.79 (0.48–1.30)

OS(KIM-1 decrease vs increase)
0.58 (0.39–0.88)
0.79 (0.46–1.35)
0.45 (0.46–0.89)

HR: hazard ratio; CI: confidence interval.