Multicenter Prospective Study of Early Predictive Biomarkers for the Efficacy of Nivolumab plus Ipilimumab in Unresectable Hepatocellular Carcinoma (HCC)

Multicenter Prospective Study of Early Predictive Biomarkers for the Efficacy of Nivolumab plus Ipilimumab in Unresectable Hepatocellular Carcinoma (HCC) PRIME HCC (Predictive Response and Immunogenetic Markers for Nivolumab plus Ipilimumab Efficacy in HCC) - PRIME HCC (Predictive Response and Immunogenetic Markers for nivolumab plus ipilimumab Efficacy in HCC)

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

JPRN

Registry ID

JPRN-UMIN000059736

Enrollment

400

Registered

2025-11-11

Start date

2025-12-01

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

unresectable Hepatocellular Carcinoma

Interventions

None listed

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1.Male or female patients aged 20 years or older who have provided written informed consent. 2.Hepatocellular carcinoma (HCC) diagnosed histologically or radiologically. 3.Planned initiation of nivolumab plus ipilimumab combination therapy as first-line or subsequent-line treatment.

Exclusion criteria

Exclusion criteria: 1.ECOG Performance Status >= 2. 2.Child-Pugh class B or C. 3.Active autoimmune disease, or a history of autoimmune disease. 4.Active second primary malignancy, including any malignancy diagnosed within the past 5 years that has not been definitively cured. 5.Requirement for systemic immunosuppressive therapy. 6.Any patient deemed inappropriate by the principal investigator or sub-investigator for reasons of safety or scientific validity.

Design outcomes

Primary

Measure	Time frame
To prospectively validate the association between Fc gamma receptor polymorphisms (primary SNP: FCGR3A V158F) and the objective response rate (ORR per RECIST v1.1) in patients with unresectable hepatocellular carcinoma (HCC) treated with nivolumab plus ipilimumab. Tumor response assessors will be blinded to SNP information to ensure independent evaluation.	—

Secondary

Measure	Time frame
Key Secondary Objectives To assess the association between Depth of Response >= 50% (DpR50) and Fc-gamma receptor SNPs. To evaluate associations of DCR, TTP, PFS, and OS with Fc-gamma receptor SNPs. To assess the predictive performance of SNPs as a practical test (e.g., sensitivity, specificity, PPV, NPV, AUC). Exploratory Objectives To explore relationships of baseline laboratory and imaging findings with ORR, DCR, DpR50, TTP, PFS, OS, and SNPs. In cases with baseline liver biopsy, to analyze tumor immune microenvironment (TIME) markers (e.g., multiplex IHC, RNA signatures) and their associations with clinical outcomes and SNPs (SNP laboratory staff blinded to clinical outcomes). Using whole blood, to perform comprehensive SNP analyses (WGS/WES) and explore immune-related variants beyond Fc-gamma receptors in relation to outcomes. To conduct pre-specified subgroup analyses by line of therapy (first-line vs. later-line). To estimate SNP allele frequencies in Japanese cancer and HCC cohorts using existing datasets and compare independently with the prospective cohort. To inform feasibility for future companion diagnostic development.	—

Measure

Time frame

Key Secondary Objectives To assess the association between Depth of Response >= 50% (DpR50) and Fc-gamma receptor SNPs. To evaluate associations of DCR, TTP, PFS, and OS with Fc-gamma receptor SNPs. To assess the predictive performance of SNPs as a practical test (e.g., sensitivity, specificity, PPV, NPV, AUC). Exploratory Objectives To explore relationships of baseline laboratory and imaging findings with ORR, DCR, DpR50, TTP, PFS, OS, and SNPs. In cases with baseline liver biopsy, to analyze tumor immune microenvironment (TIME) markers (e.g., multiplex IHC, RNA signatures) and their associations with clinical outcomes and SNPs (SNP laboratory staff blinded to clinical outcomes). Using whole blood, to perform comprehensive SNP analyses (WGS/WES) and explore immune-related variants beyond Fc-gamma receptors in relation to outcomes. To conduct pre-specified subgroup analyses by line of therapy (first-line vs. later-line). To estimate SNP allele frequencies in Japanese cancer and HCC cohorts using existing datasets and compare independently with the prospective cohort. To inform feasibility for future companion diagnostic development.

—

Countries

Japan

Contacts

Public ContactTomoko Aoki

Kindai University Faculty of Medicine Department of Gastroenterology and Hepatology

t.aoki1918@gmail.com0723660221

Outcome results