Application of immune checkpoint inhibitors in hepatocellular carcinoma: a landscape analysis of clinical trial databases.

BACKGROUND

Hepatocellular carcinoma (HCC) is a leading global malignant tumor with poor prognosis. Immune checkpoint inhibitors (ICIs) have become a breakthrough treatment for HCC, but a systematic landscape analysis of global ICI clinical trials is lacking.

METHODS

Four international clinical trial databases were systematically searched up to February 14, 2026. After screening, 132 eligible trials were included and analyzed for geographic distribution, molecular targets, clinical phases, trial status and result publication rate using R 4.5.1.

RESULTS

Trials displayed a China-US dual-core pattern (95 vs. 16). PD-1/PD-L1 inhibitors were the predominant targets, while CTLA-4 inhibitor trials were scarce. Phase II was the most frequent clinical phase (59 trials). Over 80% were interventional studies; most were recruiting or of unknown status, with only 6 terminated or withdrawn. The overall result publication rate was extremely low, with 71 PD1-targeting trials and 71.4% CTLA-4 trials were unpublished.

CONCLUSION

Global HCC ICIs trials are highly concentrated geographically and by target, with stable research progress. However, major challenges include low result translation efficiency, unbalanced target development, insufficient early/late-phase trials and uneven global collaboration. Targeted optimization is needed to promote clinical translation.