Different First-line Immunotherapy for Advancer Hepatocellular Carcinoma: A Prospective Observational Study on Efficacy and Immune Microenvironment (HCC-IM-1)

April 18, 2026 updated by: Peng Wang, Fudan University

A Prospective, Non-interventional Study of Different First-line Immunotherapy in Advanced Hepatocellular Carcinoma Patients: Efficacy and Immune Microenvironment Dynamics

To evaluate the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, non-interventional, observational study evaluating the efficacy and immune microenvironment changes in advanced hepatocellular carcinoma (HCC) patients receiving different first-line immunotherapy, including anti-PD1+anti-VEGF, anti-PD1+TKI and anti-PD1+anti-CTLA4. The primary endpoint is objective response rate (ORR), with secondary endpoints including disease control rate (DCR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and immune profiling of tumor tissue and peripheral blood before and after treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200032
        • Recruiting
        • Zhongshan Hospital, Fudan University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients with advanced hepatocellular carcinoma planed to receive first-line immunotherapy.

Description

Inclusion Criteria:

  • Age ≥ 18 years at time of study entry.
  • Barcelona Clinic Liver Cancer stage C, or stage B not amenable to curative or locoregional therapies.
  • HCC confirmed by radiology, histology or cytology.
  • No prior systemic therapy for HCC.
  • At least one measurable site of disease as defined by RECIST1.1criteria with spiral CT scan or MRI.
  • Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale).

  • Adequate organ function:

    • ANC ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL.
    • Total bilirubin ≤1.5 × ULN, AST/ALT ≤3 × ULN (≤5 × ULN if liver metastases).
    • Creatinine ≤1.5 × ULN or CrCl ≥60 mL/min.
  • Willing to provide archival/fresh tumor tissue and peripheral blood samples.
  • Signed informed consent.

Exclusion Criteria:

  • Prior systemic therapy for HCC
  • Active autoimmune disease requiring immunosuppression.
  • Active infection requiring IV antibiotics.
  • HIV-positive or active HBV/HCV infection (HBsAg+ with HBV DNA ≥2000 IU/mL; HCV RNA+).
  • Symptomatic CNS metastases.
  • Pregnancy/lactation.
  • Any condition compromising protocol compliance or data interpretation per investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
HCC cohort 1: Sintilimab plus bevacizumab biosimilar
Drug: Sintilimab
Sintilimab will be administered by IV, 200 mg every 3 weeks
Drug: Bevacizumab Biosimilar
Bevacizumab biosimilar will be administered by IV, 15 mg/kg every 3 weeks.
HCC cohort 2: Camrelizumab plus Rivoceranib
Drug: Camrelizumab
Camrelizumab will be administered by IV, 200 mg every 2 weeks.
Drug: Rivoceranib
Rivoceranib will be administered by oral 250 mg once daily.
HCC cohort 3: O+Y
Drug: Nivolumab
Nivolumab will be administered by IV, 1 mg/kg every 3 weeks for up to four doses, followed by nivolumab 480 mg every 4 weeks
Drug: Ipilimumab
Ipilimumab will be administered by IV, 3mg/kg every 3 weeks for up to four doses.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
max 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
max 24 months
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
max 24 months
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD).
max 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: max 42 months
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
max 42 months
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 42 months
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death.
max 42 months
Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
TTR is defined as the time from the start of treatment until the first objective observation of a response (either partial response, PR, or complete response, CR), provided that the response is subsequently confirmed.
max 24 months
Translational study
Time Frame: max 24 months
Proportion of different immune cell types in tumors and blood based on RNA sequencing between two groups.
max 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 21, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 28, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 21, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HCC-IM-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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