Advanced Hepatocellular Carcinoma
Conditions
Brief summary
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.
Interventions
BIOLOGICALSZ003 CAR-NK
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.
Sponsors
Guangdong ProCapZoom Biosciences Co., Ltd.
Shantou University Medical College
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. With advanced hepatocellular carcinoma (HCC) confirmed by histopathology; 2. With stage C according to the Barcelona liver cancer grading criteria (BCLC) or with stage B who are ineligible for locoregional/locoregional therapy progression; 3. Unsuitable for surgery or local therapy (including ablation, interventional and radiotherapy) and who have experienced progression or intolerance after previous standard therapy; 4. Through immune tissues chemistry, confirmation of tumor cells positive expression of relevant molecular targets (GPC3) ; 5. 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; 6. Age 18-80, male or female; 7. Karnofsky Performance Status (KPS)≥80; 8. Stable vital signs and expected survival at least 12 weeks. 9. 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; 10. Blood Routine: WBC≥2.5×109/L, PLT≥60×109/L, Hb≥9.0g/dL, LY≥0.4×109/L; 11. 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; 12. Be able to understand and sign an informed consent form
Exclusion criteria
1. With uncontrolled active infections; 2. No other prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix within 5 years before study treatment initiation. 3. With previous history of encephalopathy. 4. With active acute or chronic virus, germ infection; 5. Diagnosed with HIV infection or active hepatitis, HBV, HCV infection or other serious infectious diseases; 6. 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) ; 7. Ascites more than 5cm; 8. 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; 9. Prior solid organ transplantation or waiting for organ transplantation (including liver transplantation); 10. Prior anti-tumor therapies within 14 days before study treatment initiation, such as surgery, interventional therapy, radiotherapy, chemotherapy, immunotherapy. 11. Long-term systemic steroid therapy or patients with autoimmune diseases; 12. With a history of allergic reactions attributed to compounds of similar chemical or biological composition used in the study; 13. Have participation in clinical trials of any other investigational agents within 3 months before study treatment initiation. 14. Had received cell therapy previously but ineffective,after physical examination not allowed to received CAR-NK therapy by investigator's judgement; 15. Pregnant or lactating women; 16. Inappropriate to participate in this clinical trial by investigator's judgement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence rates and severity of AEs | through study completion, an average of 1 year | To evaluate the safety of SZ003 CAR-NK Cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall survival (OS) | up to 2 years | To determine the anti-tumor effectivity of SZ003 CAR-NK Cells |
| progression-free survival (PFS) | up to 2 years | To determine the anti-tumor effectivity of SZ003 CAR-NK Cells |
| disease control rate (DCR) and objective response rate (ORR) | up to 2 years | To determine the anti-tumor effectivity of SZ003 CAR-NK Cells |
| duration of response (DOR) | up to 2 years | To determine the anti-tumor effectivity of SZ003 CAR-NK Cells |
Countries
China
Outcome results
None listed