Single-arm, Open-label Clinical Study of SZ003 in the Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This study was a single-center, open-label, investigator-initiated clinical trial (IIT) to observe and investigate the clinical safety and efficacy of SZ003 in the treatment of advanced hepatocellular carcinoma.

Official Title
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Single-arm, Open-label Clinical Study of SZ003 in the Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: SZ003 CAR-NK


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With advanced hepatocellular carcinoma (HCC) confirmed by histopathology; With stage C according to the Barcelona liver cancer grading criteria (BCLC) or with stage B who are ineligible for locoregional/locoregional therapy progression; Unsuitable for surgery or local therapy (including ablation, interventional and radiotherapy) and who have experienced progression or intolerance after previous standard therapy; Through immune tissues chemistry, confirmation of tumor cells positive expression of relevant molecular targets (GPC3) ; With at least one stable evaluable target lesion according to RECIST 1.1 criteria, which was defined as: non-nodal lesion longest diameter ≥10 mm, or nodal lesion short diameter ≥15 mm; Age 18-80, male or female; Karnofsky Performance Status (KPS)≥80; Stable vital signs and expected survival at least 12 weeks. If HBsAg or HBcAb is positive, HBV-DNA < 200 IU/ml and to receive anti-HBV therapy ((Entecavir or tenofovirdisoproxil) for at least 14 days prior to the start of study treatment; Blood Routine: WBC≥2.5×109/L, PLT≥60×109/L, Hb≥9.0g/dL, LY≥0.4×109/L; Blood biochemistry: Alb≥30g/L, Lipase and Amylase ≤1.5 ULN, Serum creatinine ≤1.5 ULN, creatinine clearance ≥40mL/min, ALT≤5 ULN, AST≤5 ULN, Total Serum bilirubin ≤2.5 ULN, prothrombin time ≤6s; Be able to understand and sign an informed consent form Exclusion Criteria: With uncontrolled active infections; No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix within 5 years before study treatment initiation. With previous history of encephalopathy. With active acute or chronic virus, germ infection; Diagnosed with HIV infection or active hepatitis, HBV, HCV infection or other serious infectious diseases; Other serious medical conditions that may limit participation in the trial (such as poorly controlled diabetes (treated Glycated hemoglobin HbA1c > 7%) , severe heart failure (left ventricular ejection fraction (LVEF) < 45%) , myocardial infarction or unstable arrhythmia or unstable angina in the last 6 months, pulmonary embolism, chronic obstructive pulmonary disease, Interstitial lung disease, pulmonary function test FEV1 < 60% predicted, gastric ulcer, history of gastrointestinal bleeding, or definite gastrointestinal bleeding tendency) ; Ascites more than 5cm; The proportion of liver replaced by tumor≥70%, or with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver; Prior solid organ transplantation or waiting for organ transplantation (including liver transplantation); Prior anti-tumor therapies within 14 days before study treatment initiation, such as surgery, interventional therapy, radiotherapy, chemotherapy, immunotherapy. Long-term systemic steroid therapy or patients with autoimmune diseases; With a history of allergic reactions attributed to compounds of similar chemical or biological composition used in the study; Have participation in clinical trials of any other investigational agents within 3 months before study treatment initiation. Had received cell therapy previously but ineffective,after physical examination not allowed to received CAR-NK therapy by investigator's judgement; Pregnant or lactating women; Inappropriate to participate in this clinical trial by investigator's judgement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SZ003 CAR-NK<br> | Biological: SZ003 CAR-NK<br>* Drug: SZ003 CAR-NK In the escalation study, the minimum initial dose was 5.0×10^6 cells, then increased to 1.0×10^8 ,2.0×10^8 and5.0×10^8 cells. The infusion is given every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (AEs) | To evaluate the safety of SZ003 CAR-NK Cells | Up to 6 months after infusion | 
| Objective response rate (ORR) | To evaluate the ORR of SZ003 CAR-NK Cells | Up to 6 months after infusion | 
| Overall survival (OS) | To determine the anti-tumor effectivity of SZ003 CAR-NK Cells | Up to 6 months after infusion |