CHECKMATE-848

NCT03668119 📎

Regimen

Experimental
Nivolumab 240 mg IV q2w + ipilimumab 1 mg/kg IV q6w vs nivolumab 480 mg IV q4w monotherapy
Control
Nivolumab monotherapy (randomized comparison within TMB-H patients; not vs chemotherapy)

Population

TMB-H (≥10 mut/Mb by FoundationOne CDx) advanced solid tumors after ≥1 prior therapy; pan-tumor randomized basket. BTC cohort within TMB-H enrollment: not specifically segregated in primary publication; BTC proportion in pan-tumor TMB-H basket estimated ~3-5% of enrolled patients. TMB-H is distinct from MSI-H (overlap ~40-50%); BTC can be TMB-H without MSI-H. Schenker M, J Immunother Cancer 2024.

Key finding

CheckMate-848 demonstrated that TMB-H is an actionable biomarker for dual checkpoint blockade (nivo+ipi), with ORR 43.3% vs 26.0% for monotherapy — establishing combination IO as superior in TMB-H tumors. BTC-specific outcomes are not separately reported in the primary publication; given the small expected BTC fraction in a pan-tumor TMB-H basket, BTC-specific conclusions require caution. The trial indirectly supports routine TMB testing in BTC as part of comprehensive biomarker profiling, since TMB-H BTC patients may derive greater benefit from IO combination approaches.

Source: PMID 39107131

Timeline

    Guideline citations

    • NCCN BTC (p.75)