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

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.

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.

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.