Comparing first-line immunotherapy combinations for advanced liver cancer

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

We will try different first-line immunotherapy combinations to see which works best for people with advanced hepatocellular carcinoma.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07147101 on ClinicalTrials.gov

What this trial studies

This prospective, non-interventional observational study follows patients with advanced hepatocellular carcinoma who start one of several first-line immunotherapy combinations (anti‑PD‑1 plus anti‑VEGF, anti‑PD‑1 plus a TKI, or anti‑PD‑1 plus anti‑CTLA‑4). Treatment choice is made by the treating physician and the study collects imaging, clinical outcomes, and biospecimens without assigning interventions. The primary endpoint is objective response rate by RECIST 1.1, and secondary endpoints include disease control rate, duration and time to response, progression‑free survival, and overall survival. The protocol includes immune profiling of tumor tissue and peripheral blood before and after treatment to characterize changes in the tumor microenvironment.

Who should consider this trial

Good fit: Adults (≥18) with radiologic or pathologic confirmation of advanced HCC (BCLC C or unresectable B), no prior systemic therapy, at least one measurable lesion, Child‑Pugh score 5–7, ECOG ≤2, and willingness to provide tumor tissue and blood are ideal candidates.

Not a fit: Patients with prior systemic HCC therapy, uncontrolled active HBV/HCV or HIV infection, active autoimmune disease requiring immunosuppression, or poor performance status or liver function (ECOG >2 or Child‑Pugh >7) are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, the study could clarify which first‑line immunotherapy combinations produce higher tumor response rates and informative immune changes to help guide treatment choices.

How similar studies have performed: Randomized trials have demonstrated benefit for PD‑1/PD‑L1 plus anti‑VEGF combinations (for example, atezolizumab plus bevacizumab) and several PD‑1 plus TKI regimens show activity, while PD‑1 plus CTLA‑4 combinations are promising but less established.

Eligibility criteria

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Peng Wang, MD

Conditions Advanced Hepatocellular Carcinoma