Table 2 The ongoing biomarkers exploration clinical trials in the immunotherapy of hepatocellular carcinoma
NCT number (Estimated Completion Date) | Regimen | Study design (Estimated number); country | Target population | Biomarker sample | Analysis methods | Focus |
|---|---|---|---|---|---|---|
Mainly based on IHC | ||||||
NCT03753659 (June 2024) | Pembrolizumab + Local ablation (RFA, MWA, brachytherapy) | Interventional (N = 30); Germany | Histologically confirmed; Early-Stage HCC; ECOG PS of 0 or 1; Child-Pugh score of A. | Tumor tissue, blood | IHC, molecular analyses | Molecular biomarkers, immune cells, chemokines, invasion markers |
NCT04443309 (August 2024) | Lenvatinib + Camrelizumab | Interventional (N = 53); China | Histologically, cytologically, or clinically confirmed; BCLC Stage B/C; ECOG PS of 0 or 1; Child-Pugh score of A. | Tumour samples, blood | IHC, RNA-sequencing | PD-L1 expression, CD8 + T cell |
NCT04803994 (April 1, 2025) | Atezolizumab + Bevacizumab + TACE | Interventional (N = 434); Austria, Germany, Spain | Radiographic or pathologic diagnosis; intermediate-stage; Child-Pugh class A or B7; ECOG PS of 0 or 1. | Tumor, blood, stool samples | IHC, multi-omics analysis | Predictive biomarkers (tissue and circulating) for study endpoints, PD-L1 expression |
Mainly based on NGS | ||||||
NCT04701060 (February 4, 2024) | Camrelizumab + Apatinib | Interventional (N = 30); China | Clinical diagnosis resectable HCC; Child-Pugh class A; ECOG PS of 0 or 1. | Tumour samples, blood | NGS, IHC | Genomic biomarkers (TMB, TNB, ITH, HLA subtype, HLA-LOH, etc.), TILs, PD-L1 expression |
NCT04170556 (August 2024) | Regorafenib + Nivolumab | Interventional (N = 78); Spain | Histologically or clinically confirmed; Child-Pugh class A; ECOG PS of 0 or 1. | Serum and tissue | Not applicable | Serum and tissue marker characterization |
NCT04134559 (January 1, 2025) | Pembrolizumab | Interventional (N = 18); United States | Histologically confirmed; relapsed/refractory pediatric HCC | Tumor samples, blood | IHC, DNA sequencing, liquid biopsy | Dynamic changes in infiltrating immune cells, cytokines, and ctDNA; genomic biomarkers |
NCT04224636 (March 1, 2025) | Atezolizumab + Bevacizumab + TACE | Interventional (N = 106); Germany | Histologically confirmed; Child-Pugh class A or B7; ECOG PS of 0 or 1. | Tumor samples, blood, stool samples | Multi-omics analysis | Serum marker, cytokines, ctDNA, gut microbiome |
NCT04145141 (December 31, 2025) | Immunotherapy | Observational (N = 500); United States | Histologically/ultrasound/imaging confirmed | Blood, urine, and stool samples or rectal swabs | Multi-omics analysis | Genomic, genetic, and epigenetic analysis |
NCT05286320 (September 30, 2026) | Pembrolizumab + Lenvatinib + SBRT | Interventional (N = 27); Chinese Taiwan | Histologically or clinically confirmed; patients with PVTT (VP3, VP4); ECOG PS of 0. | Pre-treatment tumor samples, blood | Not applicable | Biomarkers for the response of portal vein tumor thrombosis, PFS, and OS |
NCT04246177 (December 31, 2029) | Lenvatinib + Pembrolizumab + TACE | Interventional (N = 450); Global | Radiology, histology, or cytology confirmed; HCC localized to the liver and not amenable to curative treatment; ECOG PS of 0 or 1. | Tumor samples, blood | Multi-omics analysis | Genomic, metabolic, and proteomic biomarker |
Mainly based on single-cell sequencing | ||||||
NCT05173298 (December 31, 2024) | Atezolizumab + Bevacizumab | Observational (N = 100); South Korea | Histologically, cytologically, or clinically confirmed; treatment-naïve | Tumour samples, blood | Tumor samples: H&E staining and IF staining. Blood samples: flow cytometry, ELISA, single-cell sequencing | Protein biomarker, gene-based biomarker |
NCT03419481 (December 30, 2024) | Pembrolizumab | Interventional (N = 30); Hong Kong | Confirmed diagnosis of HCC; ECOG PS of 0 or 1 | Baseline and post-treatment tumor samples (after two cycles of Pembrolizumab) | Single-cell sequencing, IHC | The serial change in cytokine profile, PD-L1 expression, TILs, the serial change in RNA expression of immune-related gene panel |
Others | ||||||
NCT03864211 (May 30, 2023) | Thermal ablation + Toripalimab | Interventional (N = 145); China | Clinically confirmed; Child-Pugh class A/B; ECOG PS of 0 or 1. | Blood samples | Liquid biopsy | Dynamic changes in inflammatory biomarkers. |
NCT05278195 (December 1, 2023) | Anti-PD-1/PD-L1 + VEGF/TKI + TACE | Observational (N = 300); China | Histologically, cytologically, or clinically confirmed; treatment-naïve | Imaging information | Radiomics artificial intelligence model | Imaging biomarkers |
NCT05044676 (September 30, 2024) | Atezolizumab + Bevacizumab | Prospectively observational (N = 120); France | Advanced HCC with an indication of systemic therapy by Atezo/Bev; ECOG PS of 0 or 1. | Blood, tumor samples (tumoral and non-tumoral liver) with dynamic monitoring | Flow cytometry | Immune cells biomarker (the frequency and phenotype expression of CD226 on CD8 + T lymphocytes and NK cells); A predictive prognostic score from histological characteristics |
NCT04368078 (April 2025) | Lenvatinib + Toripalimab | Interventional (N = 76); China | Histologically, cytologically, or clinically confirmed; BCLC Stage B/C; ECOG PS of 0 or 1; Child-Pugh score of A. | Tumor samples, blood, stool samples | Multi-omics analysis | Potential biomarkers of treatment response |
NCT04522544 (September 30, 2025) | Durvalumab + Tremelimumab + Y-90 SIRT/ TACE | Interventional (N = 84); Germany | Histologically confirmed; Child-Pugh class A; ECOG PS of 0 or 1. | Tumor tissue and blood samples | IHC, ELISA, liquid biopsy | PD-L1 expression, infiltrating immune cells, chemokines, invasion markers, circulating nucleic acids, and tumor-specific transcripts |
NCT03475953 (December 31, 2025) | Regorafenib + Avelumab | Interventional (N = 747); France | Histologically confirmed; ECOG PS of 0 or 1; Child-Pugh A. | Tumor tissue and blood samples | Liquid biopsy, IHC, liquid chromatography-mass spectrometry | Predictive blood biomarkers analysis (cytokines levels, lymphocytes); Predictive tumor growth factor biomarkers; Predictive metabolomic analysis |