Overview

This is a single-arm, phase II clinical trial evaluating the safety and efficacy of PD-L1 antibody combined with bevacizumab and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced unresectable hepatocellular carcinoma (HCC) with extrahepatic metastases.

Study Population: Patients with advanced HCC who have:

• Confirmed extrahepatic metastases
• No prior PD-L1 or bevacizumab therapy
• Age 18-75 years
• Child-Pugh A or B7 liver function
• ECOG performance status 0-1

Treatment Regimen:

• PD-L1 antibody: 1200mg every 3 weeks
• Bevacizumab: 15mg/kg every 3 weeks
• HAIC with FOLFOX regimen: Up to 6 cycles
• Treatment continues until disease progression or up to 24 months

Primary Endpoint:

-Objective Response Rate (ORR)

Secondary Endpoints:

• Disease Control Rate (DCR)
• Duration of Response (DOR)
• Progression-free Survival (PFS)
• Overall Survival (OS)
• Safety assessments
• Quality of life measurements

Study Design Details:

• Single-arm study using Simon's two-stage design
• First stage: 27 patients
• Second stage: 9 additional patients if first stage shows efficacy
• Total planned enrollment: 36 patients
• Study duration: October 2024 - July 2027

This study aims to evaluate whether adding HAIC to PD-L1 inhibitor plus bevacizumab immunotherapy can improve outcomes for advanced HCC patients with extrahepatic spread, who currently have limited treatment options. The trial will assess both efficacy and safety of this combination approach.

Eligibility

Inclusion Criteria:

Signed written informed consent Histologically/cytologically confirmed hepatocellular carcinoma (HCC) or clinically diagnosed according to HCC diagnostic criteria Radiologically confirmed extrahepatic metastases with unresectable disease as evaluated by investigators No prior treatment with PD-L1 antibody and/or bevacizumab Age ≥18 and ≤75 years ECOG Performance Status 0-1 Child-Pugh Class A or B7 Able to comply with study protocol requirements At least one measurable or evaluable lesion according to RECIST v1.1

Adequate organ and bone marrow function:

Absolute neutrophil count ≥1.5×10^9/L Platelet count ≥75×10^9/L Hemoglobin ≥9.0 g/dL Total bilirubin ≤2×ULN ALT and AST ≤5×ULN Serum creatinine ≤1.5×ULN or creatinine clearance ≥50mL/min Urine protein <2+ by dipstick APTT and INR ≤1.5×ULN Normal cardiac enzymes Normal thyroid function or on stable replacement therapy Life expectancy ≥12 weeks Effective contraception for participants of childbearing potential during treatment and for 6 months after last dose

Exclusion Criteria:

Severe complications from liver disease (severe bleeding from portal hypertension, infection, hepatic encephalopathy) Prior systemic anti-tumor therapy for HCC Other malignancy within 5 years (except adequately treated non-melanoma skin cancer or carcinoma in situ) Current participation in other interventional clinical trials Systemic treatment with Chinese herbal medicine or immunomodulators within 2 weeks before first dose Active autoimmune disease requiring systemic treatment within 2 years Systemic corticosteroid therapy within 7 days before first dose Prior allogeneic organ transplantation (except corneal) or stem cell transplantation Known allergy to monoclonal antibodies or HAIC components Inadequate recovery from prior treatment toxicities Known HIV infection Untreated active HBV infection (HBsAg positive with HBV-DNA above upper limit of normal) Active HCV infection Live vaccine administration within 30 days before first dose Pregnancy or breastfeeding

Serious or uncontrolled systemic diseases including:

Significant cardiac arrhythmias or conduction abnormalities Unstable angina or NYHA class ≥2 heart failure Arterial thrombotic events within 6 months Uncontrolled hypertension Active interstitial lung disease Active tuberculosis Active systemic infections Active diverticulitis or GI obstruction Uncontrolled diabetes Significant proteinuria Psychiatric disorders affecting compliance Any condition that could interfere with study participation or interpretation of results