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