Different First-line Immunotherapy for Advancer Hepatocellular Carcinoma: A Prospective Observational Study on Efficacy and Immune Microenvironment

Not yet recruiting

• Conditions: Advanced Hepatocellular Carcinoma (HCC)
• Interventions: Drug: Sintilimab; Drug: Camrelizumab; Drug: Nivolumab; Drug: Bevacizumab Biosimilar; Drug: Rivoceranib; Drug: Ipilimumab

• Registration Number: NCT07147101
• Lead Sponsor: Fudan University

Brief Summary

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

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 Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-21
• Study First Submitted QC: 2025-08-21
• Last Update Submitted: 2025-08-21
• Study First Posted: 2025-08-28
• Last Update Posted: 2025-08-28
• Study Start: 2025-09-01
• Primary Completion: 2028-09-01
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HCC cohort 1: Sintilimab plus bevacizumab biosimilar	Sintilimab	-
HCC cohort 1: Sintilimab plus bevacizumab biosimilar	Bevacizumab Biosimilar	-
HCC cohort 2: Camrelizumab plus Rivoceranib	Camrelizumab	-
HCC cohort 2: Camrelizumab plus Rivoceranib	Rivoceranib	-
HCC cohort 3: O+Y	Nivolumab	-
HCC cohort 3: O+Y	Ipilimumab	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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.

Secondary Outcome Measures

Name	Time	Method
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	max 24 months	DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD).
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	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.
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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.
Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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.
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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)
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1	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.
Translational study	max 24 months	Proportion of different immune cell types in tumors and blood based on RNA sequencing between two groups.

Trial Locations

Locations (1)

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai Municipality, China