Circulating KIM-1 is a minimally invasive biomarker correlated with treatment response to nivolumab in patients with metastatic renal cell carcinoma

Abstract

Abstract Background There are currently no circulating biomarkers used for clinical monitoring of clear cell renal cell carcinoma (ccRCC). Such a biomarker could facilitate individualized treatment decisions and minimize exposure to ineffective therapies. Prior studies have suggested that circulating KIM-1 is a potential minimally invasive biomarker for ccRCC, but the utility of KIM-1 for identifying early response to nivolumab therapy is not known. Methods CheckMate-009 was a prospective trial investigating nivolumab (every 3 weeks at 0.3, 2, or 10 mg/kg) in patients with metastatic clear cell RCC. We measured serum KIM-1 at baseline and after 3 weeks of treatment (prior to cycle 2) using a custom sandwich immunoassay using the R-PLEX platform. Human KIM-1 antibody (R&D systems, #AF1750) was used to prepare biotin conjugated antibodies and detection antibodies. The assay lowest limit of detection for KIM-1 was 4.88 pg/mL. We assessed the association between early changes in serum KIM-1 and treatment related clinical outcomes. Results Clinical data and serum KIM-1 was analyzed in 54 patients. KIM-1 was high in all patients at baseline (median serum KIM-1 5913 pg/mL, IQR 2137-25101 pg/mL). 25 patients (48%) had a decrease in KIM-1 at 3 weeks after a single dose of nivolumab. Decrease in KIM-1 at 3 weeks was associated with improved PFS (univariable HR 0.26, 95% CI 0.13-0.52; multivariable HR 0.22, 95% CI 0.097-0.50 after adjustment for sex, prior nephrectomy, nivolumab dose, and IMDC risk factors). Conclusions Serum KIM-1 is elevated in patients with metastatic ccRCC and is associated with clinical outcomes. Among patients treated with nivolumab in the CheckMate-009 trial, early decrease in KIM-1 from baseline to 3 weeks was predictive for PFS. CDMRP DOD Funding: yes