UMIN-ICDS Clinical Trial

Public title

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

Acronym

PRIME HCC (Predictive Response and Immunogenetic Markers for nivolumab plus ipilimumab Efficacy in HCC)

Scientific Title

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)

Scientific Title:Acronym

PRIME HCC (Predictive Response and Immunogenetic Markers for nivolumab plus ipilimumab Efficacy in HCC)

Region

Japan

Condition

unresectable Hepatocellular Carcinoma

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To determine whether Fc gamma receptor polymorphisms (primary SNP: FCGR3A V158F) function as early predictive biomarkers of efficacy for nivolumab plus ipilimumab in unresectable HCC, within a multicenter prospective design with response assessors blinded to SNP information, and to define a clinically usable decision rule.

Basic objectives2

Others

Basic objectives -Others

To develop an integrated prediction model combining SNPs with clinical/laboratory and imaging features and tumor immune microenvironment (TIME) markers, and to perform internal validation.
To assess applicability across clinical subgroups (e.g., line of therapy: first-line vs later-line, and use of locoregional therapy).
To estimate Fc gamma receptor SNP allele frequencies in Japanese cancer/HCC cohorts using existing datasets and compare independently with the prospective cohort.
To generate evidence supporting the feasibility of a future companion diagnostic.

Trial characteristics_1

Confirmatory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

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.

Key secondary outcomes

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.

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key 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.

Key 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.

Target sample size

400

Name of lead principal investigator

1st name	Masatoshi
Middle name
Last name	Kudo

Organization

Kindai University Faculty of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

589-8511

Address

377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan

TEL

+81-72-366-0221

Email

m-kudo@med.kindai.ac.jp

Name of contact person

1st name	Tomoko
Middle name	Tomoko
Last name	Aoki

Organization

Kindai University Faculty of Medicine

Division name

Department of Gastroenterology and Hepatology

Zip code

5898511

Address

377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan

TEL

0723660221

Homepage URL

Email

t.aoki1918@gmail.com

Institute

Kindai University

Institute

Department

Personal name

Organization

Departmental Research Allocation Fund

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kindai University Faculty of Medicine Ethics Committee

Address

377-2 Ohno-higashi Osaka-Sayama, Osaka, Japan

Tel

0723660221

Email

zizen@med.kindai.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2025

Year

11

Month

11

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2025

Year

11

Month

11

Day

Date of IRB

Anticipated trial start date

2025

Year

12

Month

01

Day

Last follow-up date

2030

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study is a prospective, multicenter observational study evaluating the association between treatment response to nivolumab plus ipilimumab for unresectable hepatocellular carcinoma and Fc gamma receptor (FCGR) genetic polymorphisms. All treatments are provided as part of routine clinical practice, and no additional interventions are performed. Peripheral blood samples are collected at registration for FCGR3A (CD16) V158F genotyping. Treatment outcomes, including objective response rate and depth of response assessed by RECIST 1.1, progression-free survival, overall survival, and immune-related adverse events, are prospectively recorded. Tumor immune microenvironment analysis (pathology and RNA-based exploratory profiling) is conducted as exploratory research.
Ethics committee approval is currently pending. Preparatory activities, including study briefings and operational setup at participating sites, are in progress. Patient enrollment has not yet commenced.

Registered date

2025

Year

11

Month

11

Day

Last modified on

2025

Year

11

Month

11

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000067480