CheckMate 214: Evaluating KIM-1 as a Biomarker in Advanced RCC

Increased levels of baseline circulating kidney injury marker-1 (KIM-1) are associated with worse clinical outcomes for patients receiving nivolumab plus ipilimumab (nivo/ipi) or sunitinib alone in the CheckMate 214 study, according to research presented at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium.

Results were presented by Wenxin Xu, MD, of Dana-Farber Cancer Institute and Harvard Medical School.

Previous readouts of CheckMate 214 established nivo/ipi as a first-line standard-of-care regimen for advanced renal cell carcinoma (aRCC) after demonstrating superior survival and durable response rates compared with sunitinib. High levels of circulating KIM-1 are known to be associated with worse prognosis, and reduction in KIM-1 levels is associated with benefit from adjuvant immunotherapy.

Dr. Xu and colleagues conducted a post hoc analysis to evaluate whether KIM-1 levels at baseline and after one cycle of nivo/ipi or sunitinib are associated with treatment outcomes in CheckMate 214. Serum KIM-1 was measured at baseline as well as at three weeks after first treatment dose through use of an enzyme-based electrochemiluminescence assay. Researchers evaluated the association between KIM-1 levels and clinical outcomes through Kaplan-Meier and Cox proportional hazards analyses.

Serum samples from 821 patients were analyzed, including 75% of the Checkmate 214 intention-to-treat population. Median KIM-1 level at baseline was 660.4 pg/mL.

Dr. Xu and colleagues reported that across both arms, higher KIM-1 levels were associated with shorter overall survival (OS) independent of International mRCC Database Consortium risk group, nephrectomy status, and tumor burden.

In addition, they found that a decrease in KIM-1 from baseline to day 1 of their second treatment cycle was strongly associated with progression-free survival (PFS) and OS among patients who received nivo/ipi. The median PFS was 70.8 months compared with 4.2 months for patients with a decrease of more than 30% in KIM-1 and patients with an increase of more than 30% in KIM-1, respectively. The median OS was 85.4 months versus 26.6 months, respectively, and the overall response rate was 69.3% versus 13.9%, respectively.

This trend of decreasing KIM-1 from baseline to day 1 of the second treatment cycle being associated with PFS and OS was not found for patients who received sunitinib, researchers noted.

“In CheckMate 214, increased levels of baseline circulating KIM-1 were associated with worse clinical outcomes,” Dr. Xu and colleagues concluded. “The extent of reduction in serum KIM-1 just 3 weeks after a single cycle of nivo/ipi was associated with long term efficacy of this immunotherapy doublet.”

“Circulating KIM-1 may be a useful minimally invasive biomarker for monitoring patients on RCC immunotherapy,” they added.