KIM-1 levels in papillary renal cell carcinoma from the CALYPSO trial.

557 Background: Kidney Injury Molecule-1 (KIM-1) has emerged as a promising biomarker in clear cell renal cell carcinoma (RCC), but its role in papillary RCC remains unknown. Methods: Serum KIM-1 concentrations were analyzed in patients with papillary RCC (n=32) and clear cell RCC (n=123) enrolled in a prospective randomized phase II trial evaluating durvalumab plus savolitinib (D+S) for papillary RCC. Associations between KIM-1 and clinicopathologic or molecular features were evaluated. Longitudinal changes in KIM-1 with time were correlated with radiologic response, circulating tumor DNA (ctDNA) status and molecular subgroups. Results: The median KIM1 levels for patients (n=32) with papillary RCC who received D+S was 7835 pg/mL. This was significantly higher than the clear cell RCC cohort (n=123) at baseline (5470 pg/mL, p=0.05). Other comparisons between these cohorts are shown in Table 1. In the papillary cohort, higher baseline KIM-1 levels did not correlate with the IMDC score, PD-L1 or TMB, but were lower in MET-driven tumors compared to non-MET driven (4217 vs 19834 pg/mL, p=0.05). Radiological response was associated with lower baseline KIM-1 levels (3368 vs 14154 pg/mL in non-radiological responders, p=0.025). Sequential KIM-1 results (n=19) showed a 54% decrease in radiological responders vs a 7% decrease in non-radiological responders (59% vs 11% in MET vs non-MET driven tumors). ctDNA positivity correlated with higher KIM-1 concentrations (17448 vs 5226 pg/mL in ctDNA-negative), and the combination of ctDNA positivity and elevated KIM-1 identified patients with poorer outcomes. Conclusions: KIM-1 levels are raised in papillary RCC. They correlated with tumor biology, MET status and response to treatment. Clinical trial information: NCT02819596 . Baseline serum KIM-1 levels according to clinical characteristics in papillary and clear cell RCC. Papillary RCC Clear cell RCC Baseline levels (pg/mL) 7835 5470 IMDC poor risk 40127 7998 IMDC intermediate risk 5918 6045 IMDC good risk 9789 4420 No prior nephrectomy 2282 9800 Prior nephrectomy 8705 5000 Presence of liver metastases 21321 6783 Absence of liver metastases 4791 5416