Advanced Hepatocellular Carcinoma Following Failure of First-Line Treatment
Conditions
Interventions
Phase I —Experimental Group :CL002NK cell infusion, with a cell dose of 1 × 10^9,2×10^9,5×10^9 cells per infusion.
Phase ? —Experimental Group :CL002NK cell infusion, with the cell dose determined based on the optimal dose obtained from Phase I.
Sponsors
The Third Affiliated Hospital of Naval Medical University
Eligibility
Sex/Gender
All
Age
20 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily agree to participate in the study, have signed the informed consent form (ICF), and are able to comply with study visits and related procedures. 2. Male or non-pregnant female patients aged between 20 and 70 years. 3. Histologically confirmed diagnosis of hepatocellular carcinoma (HCC), based on the 2024 CSCO guidelines for the diagnosis and treatment of primary liver cancer. 4. BCLC stage B or C unresectable HCC, including patients with disease progression after surgery/local therapy or those who are ineligible for such treatments; recurrent or metastatic HCC; or those intolerant of or not benefiting from standard first-line treatments. 5. Disease progression following at least one prior first-line systemic therapy, with prior exposure to PD-1/L1 inhibitors and/or tyrosine kinase inhibitors. 6. Child-Pugh class A liver function, or class that can be improved to class A with treatment, with no history of hepatic encephalopathy. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 within 7 days prior to enrollment. 8. Estimated life expectancy of at least 12 weeks. 9. At least one measurable lesion per RECIST v1.1 criteria (a measurable lesion is defined as one with a longest diameter =10 mm on CT/MRI or short axis =15 mm for lymph nodes, unless radiologic evidence confirms unequivocal progression). 10. GPC-3 positivity confirmed by investigators. Tumor tissue samples must be available. Samples must be either fresh or archived tumor tissues obtained within 2 years prior to ICF signing. Preferably, one formalin-fixed paraffin-embedded (FFPE) tumor block, or 5–10 unstained consecutive sections on positively charged glass slides, should be provided if previously collected via surgery or biopsy. 11. Patients must have adequate organ and bone marrow function as defined by the following laboratory criteria: Bone marrow function: • Absolute neutrophil count (ANC) >= 1.5 × 10?/L • Platelet count (PLT) >= 75 × 10?/L (no transfusion or stimulating factors allowed within 14 days prior to screening) • Hemoglobin >= 90 g/L Liver function: • Total bilirubin = 60 mL/min (calculated using the Cockcroft-Gault formula) Coagulation function: • INR <= 1.5 × ULN • APTT <= 1.5 × ULN (patients on prophylactic anticoagulation must have INR between 2.0 and 3.0) 12. Negative HIV antibody test at screening. 13. Patients with active hepatitis B virus (HBV) infection must have HBV DNA < 500 IU/mL within 28 days before study treatment initiation and have received at least 14 days of antiviral therapy prior to enrollment (according to local standard treatment such as entecavir) and be willing to continue antiviral therapy throughout the study period. 14. Women of childbearing potential must have a negative pregnancy test (ß-HCG) before initiating treatment. Both women of childbearing potential and men with partners of childbearing potential must agree to use effective contraception continuously during the treatment period and for 6 months after the last dose of study treatment.
Exclusion criteria
Exclusion criteria: 1. Metastasis to the central nervous system, including brain metastases and/or meningeal metastases; 2. History of prior bone marrow or organ transplantation (including but not limited to liver transplantation) or awaiting transplantation; 3. History of other tumors or patients with multiple primary tumors; 4. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA > 500 IU/mL (detection limit; HBV DNA = grade 3 cardiovascular events occurring within 6 months prior to screening; • Heart failure classified as NYHA functional class >= II or left ventricular ejection frac
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity, DLT;Adverse Events, AEs; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR;Progression-Free Survival, PFS;Disease control rate, DCR;Overall Survival, OS;Quality of Life; | — |
Countries
China
Contacts
Public ContactCheng Shuqun
The Third Affiliated Hospital of Naval Medical University
Outcome results
None listed