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

Area of Science:

• Nephrology
• Oncology
• Biomarker Discovery

Background:

• Kidney injury molecule 1 (KIM-1) is a potential biomarker for clear cell renal cell carcinoma (ccRCC).
• Its role in advanced ccRCC and papillary RCC (pRCC) is not well-defined.
• The CALYPSO trial investigated novel therapies for metastatic RCC.

Purpose of the Study:

• To explore if KIM-1 levels are elevated in pRCC compared to ccRCC.
• To assess the association of KIM-1 with treatment response and survival in advanced ccRCC and pRCC.
• To evaluate KIM-1 as a prognostic biomarker in metastatic renal cell carcinoma.

Main Methods:

• Prospective, multi-arm CALYPSO trial (NCT02819596) involving durvalumab, tremelimumab, or savolitinib.
• Measurement of circulating KIM-1 levels at baseline and during treatment.
• Exploratory analyses correlating KIM-1 levels with tumor type, treatment response, progression-free survival (PFS), and overall survival (OS).

Main Results:

• Higher median KIM-1 concentrations were observed in pRCC versus ccRCC (p=0.05).
• Systemic therapy reduced KIM-1 levels in both ccRCC (-59.2%) and pRCC (-32%).
• In pRCC, responders had lower baseline KIM-1 (p=0.025). In ccRCC, high baseline KIM-1 correlated with shorter OS (HR 1.77, p=0.01), and increased KIM-1 during therapy linked to worse PFS and OS.

Conclusions:

• Circulating KIM-1 levels are higher in pRCC compared to ccRCC.
• KIM-1 demonstrates utility as a prognostic biomarker in advanced ccRCC and pRCC.
• KIM-1 changes during therapy may predict treatment outcomes in ccRCC.