Dr Pal on the Predictive Utility of KIM-1 Expression in High-Risk Resected RCC

"When we look at baseline specimens, we can identify, for instance, patients that have an angiogenic profile or a T-effector profile, which...is associated with immunotherapy sensitivity. We don't necessarily see a direct association with benefit from atezolizumab."

Sumanta Kumar Pal, MD, FASCO, chair of the Kidney and Bladder Cancer Disease Team, co-director, Kidney Cancer Program, professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses the potential use of serum KIM-1 levels as a biomarker for clinical benefit or recurrence risk in patients with high-risk, resected renal cell carcinoma (RCC).

Findings from comprehensive tissue and blood biomarker analyses from the phase 3 IMmotion010 trial (NCT03024996), a randomized study evaluating adjuvant atezolizumab (Tecentriq) vs placebo, were presented during the 2025 ASCO Annual Meeting and indicated that serum KIM-1 levels may hold prognostic and predictive value. In the KIM-1–high subgroup (n = 151 for atezolizumab; n = 149 for placebo), disease-free survival (DFS) was longer with atezolizumab vs placebo (not estimable [NE] vs 21.16 months; HR, 0.72; 95% CI, 0.52-0.99). No DFS benefit was observed in the KIM-1–low subgroup (n = 229 for atezolizumab; n = 223 for placebo).

According to Pal, these results represent the first comprehensive biomarker dataset from an adjuvant immunotherapy study in kidney cancer, offering important context for patient stratification. Analysis of immune and angiogenic signatures revealed that most patients exhibited an angiogenic profile, with a subset displaying a T-effector immune-related signature.

Access to tumor samples from patients at the time of progression allowed for additional mechanistic insights, including the downregulation of major histocompatibility complex class I (MHC-I) pathways observed at recurrence, suggesting potential resistance to immunotherapy.

Pal emphasized that integrating baseline genomic characteristics, serum biomarkers such as KIM-1, and molecular profiling of recurrent tumors could guide future strategies to identify patients most likely to benefit from adjuvant therapy and to develop approaches that overcome immune resistance in high-risk RCC.