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

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: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Camrelizumab; Drug: Sintilimab; Drug: Bevacizumab Biosimilar; Drug: Rivoceranib; Drug: Nivolumab; Drug: Ipilimumab

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: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Peng Wang, MD; Phone Number: 86-21-64041990; Email: peng_wang@fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • Zhongshan Hospital, Fudan University
      • Contact: Peng MD, Wang; Phone Number: +86021-64041990; Email: peng_wang@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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	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	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	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	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	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	Proportion of different immune cell types in tumors and blood based on RNA sequencing between two groups.	max 24 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: August 21, 2025
• First Submitted That Met QC Criteria: August 21, 2025
• First Posted (Actual): August 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 18, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab; camrelizumab; sintilimab; apatinib
• Other Study ID 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