Tumor and peripheral biomarker analysis from the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib for advanced renal cell carcinoma
Integrative tumor immunohistochemical, genomic, and transcriptomic analyses found T cell density, SETD2 mutational status, high inflammatory response and oxidative stress to be associated with NIVO+CABO outcomes versus sunitinib. EMT and CAF pathways were associated with resistance to NIVO+CABO. Further, clinical outcomes were improved with NIVO+CABO versus sunitinib across 6 transcriptomically-defined clusters; T-effector/proliferative cluster was enriched for c-MET positivity which differentiated NIVO+CABO outcomes. Among circulating factors, high IL-6, TN-C, and TIMP-1 were predictive of NIVO+CABO outcomes versus SUN. NIVO+CABO increased levels of cytokines associated with immune activation/inflammation/oxidative stress These results support metabolic/immune pathway activation within the tumor and peripheral circulation as possible contributors to PD-1 based efficacy.
Type: Cancer Genomics
Archive: European Genome-phenome Archive (EGA)
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