| Eligibility |
Inclusion Criteria:
- All subjects must meet all of the following criteria to be eligible for enrollment in
this study:
1. Aged 18-75 years, male or female;
2. Subjects with histopathologically or cytologically confirmed advanced
hepatocellular carcinoma (HCC) who are ineligible for surgery or local therapy,
have progressed or being intolerant to prior standard systemic therapies
(systemic therapies include but are not limited to systemic chemotherapy and
molecular targeted therapy), or those who have no effective treatment options at
the time of enrollment as judged by the investigator;
3. Subjects with at least one stable and evaluable intrahepatic or extrahepatic
target lesion (longest diameter of non-nodal lesions = 10 mm, or short axis of
lymph node lesions = 15 mm) at enrollment as per RECIST V1.1 criteria;
4. Subjects with GPC3 positive (> grade 2) tumor tissue samples (> 25% tumor cells
positive staining) as tested by immunohistochemistry (IHC);
5. Subjects with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular
carcinoma, or subjects with BCLC Stage B hepatocellular carcinoma who are not
amenable to local therapy or have progressed after local therapy;
6. Subjects with expected survival > 12 weeks;
7. Subjects with liver cirrhosis of Child-Pugh grade A (5-6 points);
8. Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1;
9. Subjects with inactive hepatitis B (if HBsAg or HBcAb is positive, then HBV-DNA
must be < 20 IU/mL, and HBsAg-positive patients should have been treated with
antiviral therapies as per the Guidelines for the Prevention and Treatment of
Chronic Hepatitis B (2019 Edition));
10. The largest diameter of intrahepatic tumors is < 10 cm, and the number of
multiple tumors is < 10 (if pulmonary metastatic lesions are present, the number
of metastatic lesions is < 6);
11. Subjects with a venous access for mononuclear cell collection;
12. Subjects with adequate bone marrow function that allows for lympho-depleting
pre-conditioning and without contraindications for the pre-conditioning as
assessed by the investigator;
13. Subjects with liver, kidney, respiratory, cardiovascular functions, and
corresponding hematological levels as defined below:
1. Alanine aminotransferase (ALT) = 5.0 × ULN, aspartate aminotransferase (AST)
= 5.0 × ULN, and total bilirubin = 2.5 × ULN at screening;
2. Requirements for blood coagulation at screening: prothrombin time (PT)
prolongation = 4 s, fibrinogen = 1 g/L, activated partial thromboplastin
time (APTT) = 1.5 × ULN;
3. Serum creatinine = 1.5 × ULN or endogenous creatinine clearance > 50 mL/min
(Cockcroft-Gault formula) at screening;
4. Pulmonary function at screening: finger oxygen saturation = 95% at screening
and prior to apheresis;
5. Cardiac function at screening: left ventricular ejection fraction (LVEF) =
50% as assessed by echocardiography within 1 month;
6. Subjects with white blood cell count = 3.0×109/L and lymphocyte count =
0.5×109/L at screening (except for those receiving bridging chemotherapy),
platelet count = 75×109/L, hemoglobin = 90 g/L, and neutrophil count =
1.5×109/L (this criterion should also be met within 24 hours prior to
apheresis).
14. Female subjects of childbearing potential (all women physiologically capable of
becoming pregnant) must have a negative serum pregnancy test both at screening
and within 14 days prior to the first dose and are willing to use reliable
contraception methods during the study (within 24 months after the first dose of
cell infusion). For male subjects whose partners are women of childbearing
potential, the subjects should have been surgically sterilized or agree to use
reliable contraception methods during the study as well as for additional 1 year
after receiving the last study treatment;
15. Subjects with ability to understand and sign the Informed Consent Form.
Exclusion Criteria:
- Subjects who meet any of the following criteria cannot participate in this study:
1. Having other uncured malignancies (except cervical carcinoma in situ and basal
cell carcinoma of skin) within the past 5 years or at present, or hepatocellular
carcinoma with brain metastases;
2. With a history of any of the following cardiovascular diseases within the past 6
months: New York Heart Association (NYHA) Grade III or IV heart failure, cardiac
angioplasty or stenting, myocardial infarction, unstable angina, or other
clinically significant heart diseases, or poorly controlled high blood pressure
(systolic blood pressure > 150 mm Hg, or diastolic blood pressure > 90 mm Hg), or
hypotension that requires treatment with vasopressors;
3. With metastases to the central nervous system (CNS) and clinically significant
CNS disorders; with prior or clinically significant CNS diseases at screening,
such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain injury,
dementia, Parkinson's disease, cerebellar disease, brain organic syndrome or
psychiatric disorder;
4. With prior hepatic encephalopathy or at present;
5. With a history of serious lung diseases, including pulmonary embolism, chronic
obstructive pulmonary disease, interstitial lung disease and clinically
significant abnormal findings in pulmonary function tests;
6. With an active infection (uncontrolled active infections caused by bacteria,
viruses, or fungus requiring systemic therapy) at screening, or has an
unexplained fever of = 38.0 °C during screening or prior to the first dose;
7. With known active autoimmune diseases requiring immunosuppressive therapy,
including biologics;
8. With a history of organ transplantation or awaiting organ transplantation
(including liver transplantation);
9. With = 50% of liver replaced by tumor, or with the main portal vein tumor
thrombus, or the mesenteric vein/inferior vena cava has been invaded by tumor
thrombus;
10. With a co-infection of HBV and HCV viruses or infections caused by more than two
viruses;
11. Positive HCV-RNA, HIV antibody, or syphilis serology, or any other uncontrollable
active infections;
12. Requiring long-term antiplatelet therapy (aspirin > 300 mg/day; clopidogrel > 75
mg/day);
13. Have received prior cell-based therapies such as targeted GPC3 therapy, TCR-T
therapy, CAR-T therapy;
14. With moderate or higher amount of pleural effusion/ascites with clinical
symptoms, or have undergone drainage of pleural effusion/ascites within the past
month (except for those with only small amounts of pleural effusion/ascites
revealed by imaging examinations but without symptoms);
15. With active bleeding or coagulation test abnormalities, bleeding tendency or
undergoing thrombolytic, anticoagulant, or antiplatelet therapy (except those
requiring heparin due to PICC or deep vein catheterization), or massive
bleeding/blood loss (greater than 450 mL) within 28 days;
16. With a history of gastrointestinal bleeding within 3 months or definite tendency
of gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal
occult blood positive);
17. Having received any of the following treatments:
1. Have received supportive care such as blood transfusion, platelet
transfusion, cell growth factors (except recombinant erythropoietin) within
2 weeks prior to apheresis:
2. Have received anti-PD-1/PD-L1 monoclonal antibody treatment within 4 weeks
prior to apheresis;
3. Have used any study drug within 4 weeks prior to apheresis, except those who
have failed to respond to the study treatment or have experienced disease
progression during study treatment and at least 3 half-lives have passed
prior to peripheral blood mononuclear cell collection);
4. Have undergone any surgical treatment, interventional therapy,
chemoradiotherapy, ablation, targeted therapy, treatments with invasive
investigational medical devices, or are receiving immunomodulatory therapy
for the disease under study within 2 weeks prior to apheresis;
5. With prior use of prednisone at doses = 15 mg /day (or equivalent
glucocorticoids) systemically within 2 weeks prior to apheresis, or may
require long-term glucocorticoid therapy during study treatment as judged by
the investigator (except those who have recently or are currently using
inhaled or topical glucocorticoids);
6. Have received any Chinese herbal medicine or Chinese patent medicine to
control liver cancer within 2 weeks prior to apheresis.
18. With previous allergic reactions to immunotherapy, have received related drugs
(such as tocilizumab, cyclophosphamide), or excipients or matrix components
contained in B010-A for Injection (e.g., albumin, dimethyl sulfoxide, etc.);
19. Toxicities caused by prior treatments have not recovered to CTCAE Grade = 1,
except for alopecia and other events judged as tolerable by the investigator;
20. Unable or unwilling to comply with protocol requirements as judged by the
investigator.
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