Actively Recruiting
A Phase 1/2, Open-Label, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target GPC3/B7-H3 (CD276) CAR Natural Killer Cells in Adults With Advanced Unresectable or Metastatic Hepatocellular Carcinoma
Led by Beijing Biotech · Updated on 2026-03-30
30
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating an investigational allogeneic dual-target CAR-NK cell therapy aimed at treating adults with advanced hepatocellular carcinoma (HCC). This therapy targets two antigens, GPC3 and B7-H3, to address tumor cell heterogeneity and reduce antigen escape. The study is designed as a phase 1/2 open-label trial focusing first on safety and dose-limiting toxicities, then expanding at the recommended phase 2 dose to estimate preliminary anti-tumor activity. It addresses a patient population with unresectable, relapsed/refractory, or metastatic HCC who have limited treatment options. Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before an intravenous infusion of the genetically engineered CAR-NK cells. The trial uses a dose-escalation approach in phase 1 to find the safe dose, followed by a dose-expansion phase 2 at the recommended dose. Close monitoring for infusion reactions, cytokine release syndrome, neurotoxicity, hepatotoxicity, cytopenias, infections, and off-tumor effects is implemented throughout the study. During the study, participants undergo serial imaging and translational assessments such as CAR-NK cell persistence, serum AFP levels, cytokine profiling, and circulating tumor DNA dynamics. Safety is monitored for at least 12 months, including tracking dose-limiting toxicities and adverse events. Efficacy outcomes include response rates, disease control, duration of response, progression-free survival, and overall survival. The total participation duration varies with these assessments and ongoing safety follow-up.
CONDITIONS
Brief Title
Dual-Target GPC3/B7-H3 CAR-NK Cells for Advanced HCC
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 to 75 years
- Confirmed hepatocellular carcinoma by biopsy or imaging with tissue confirmation of target expression
- Unresectable, locally advanced, or metastatic HCC not suitable for surgery, transplant, or further locoregional therapy
- Disease progression on or intolerance to at least one prior systemic treatment
- Tumor expression of GPC3 in ≥25% of viable cells and B7-H3 in ≥10% of tumor or stromal cells
- At least one measurable lesion by RECIST 1.1
- ECOG performance status of 0 or 1
- Child-Pugh class A or stable B7 without uncontrolled ascites or recent encephalopathy
- Estimated life expectancy of at least 12 weeks
- Adequate organ function including blood counts and liver/kidney tests
- Controlled hepatitis B or C infection if present
- Negative pregnancy test for participants of childbearing potential and agreement to use contraception
- Ability to understand and sign informed consent
You will not qualify if you...
- Prior gene-modified cellular therapy with unresolved toxicity
- Active, uncontrolled infections including HIV, HBV, HCV with high viral load, or tuberculosis
- Active CNS metastases requiring urgent treatment
- History of liver or other solid-organ transplant or need for chronic immunosuppression
- Significant ascites, hepatic encephalopathy, or recent major bleeding
- Extensive liver tumor burden or major vascular obstruction increasing treatment risk
- Recent major surgery, radiotherapy, or systemic therapy too close to lymphodepletion
- Active autoimmune disease requiring systemic immunosuppression
- Serious cardiovascular, pulmonary, or other comorbid conditions increasing risk
- Pregnant or breastfeeding
- Other active malignancies requiring treatment
- Any medical or psychiatric condition that may compromise safety or study compliance
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for eligibility confirmation and biomarker testing
Duration - Treatment period includes lymphodepletion and CAR-NK infusion with follow-up for 28 days to monitor dose-limiting toxicities.
Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by infusion of allogeneic dual-target GPC3/B7-H3 CAR-NK cells.
Multiple visits during the first month including chemotherapy administration, CAR-NK infusion, and close safety monitoring
Duration - Up to 12 months after treatment
Participants undergo protocol-defined safety monitoring, serial imaging, and translational assessments including CAR-NK persistence and biomarker analysis.
Regular visits for safety assessments and imaging over 12 months
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
Seni S Lu, Phd
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
1
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