KIM-1 in Advanced Papillary and Clear Cell Renal Cell Carcinoma

Kidney injury molecule 1 (KIM–1) is a promising circulating biomarker in advanced renal cell carcinoma (RCC), including papillary histology, a population in which validated biomarkers are currently lacking. Plasma KIM–1 levels are higher in patients with advanced papillary and clear cell RCC compared to levels previously reported in localized disease. High baseline KIM–1 levels are prognostic in advanced clear cell RCC and potentially in papillary RCC. Dynamic declines in circulating KIM–1 during therapy correlate with radiological response in both clear cell and papillary subtypes, suggesting value for real–time disease monitoring. KIM-1 may have a future role as an early treatment-monitoring biomarker, supporting real-time assessment of therapeutic benefit. Standardization of assay methodology and definition of clinically meaningful thresholds are essential steps toward integrating KIM–1 into biomarker–guided therapy for advanced RCC. Kidney injury molecule 1 (KIM-1) is a promising biomarker in adjuvant clear cell renal cell carcinoma (ccRCC), but its relevance in advanced ccRCC or papillary RCC (pRCC) remains unclear. CALYPSO (NCT02819596) was a prospective, multi-arm trial that evaluated durvalumab alone or in combination with tremelimumab or savolitinib in metastatic ccRCC and pRCC. Circulating KIM-1 levels were measured at baseline and on-treatment. The primary endpoint was to explore if KIM-1 levels were raised in pRCC. Analyses were exploratory and p values were nominal. KIM-1 was measured in 123 patients with ccRCC and 31 patients with pRCC. Higher median concentrations occurred in pRCC compared to ccRCC (7835 vs 5470 pg/ml, p = 0.05). Reductions in KIM-1 levels occurred with systemic therapy in both ccRCC and pRCC (−59.2% and −32% respectively). In pRCC, radiological responders had significantly lower baseline KIM-1 levels ( p = 0.025). In ccRCC, high baseline KIM-1 levels were associated with significantly shorter overall survival (OS) (hazard ratio [HR] 1.77; 95% CI, 1.15–2.72; p = 0.01). Also, an increase in KIM-1 during therapy was linked to worse progression-free survival (HR 1.7; 95% CI, 1.13–2.58; p = 0.01) and OS (HR 1.95; 95% CI, 1.23–3.08; p = 0.004) in ccRCC. This exploratory analysis supports the utility of KIM-1 in advanced ccRCC and pRCC.