Dual-target GPC3 and B7-H3 CAR‑NK therapy for advanced liver cancer
A Phase 1/2, Open-Label, Dose-Escalation and Dose-Expansion Study of Allogeneic Dual-Target GPC3/B7-H3 (CD276) Chimeric Antigen Receptor Natural Killer Cells in Adults With Unresectable, Relapsed/Refractory, or Metastatic Hepatocellular Carcinoma
This trial will test an off‑the‑shelf CAR‑NK cell therapy that targets GPC3 and B7‑H3 in adults with advanced hepatocellular carcinoma who have progressed on or cannot take standard treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07500220 on ClinicalTrials.gov |
What this trial studies
This is a phase 1/2, single‑group trial of an allogeneic donor‑derived NK cell product engineered with a dual CAR against GPC3 and B7‑H3, given after standard fludarabine/cyclophosphamide lymphodepletion. Phase 1 uses dose escalation to define safety, dose‑limiting toxicities, and the recommended phase 2 dose, and phase 2 expands at that dose to estimate preliminary activity. Enrollment requires tumor tissue showing GPC3 and B7‑H3 expression above prespecified cutoffs and measurable disease by RECIST 1.1, with careful hepatic function and performance-status eligibility. Clinical endpoints center on safety and feasibility in phase 1 and early anti‑tumor responses and durability in phase 2.
Who should consider this trial
Good fit: Ideal candidates are adults 18–75 with unresectable or metastatic HCC who have progressed on or are ineligible for standard systemic therapy, have GPC3 expression ≥25% and B7‑H3 ≥10% on tumor/tumor‑associated cells, ECOG 0–1, and adequate liver function (Child‑Pugh A or stable B7).
Not a fit: Patients lacking the required GPC3 and B7‑H3 tumor expression, with poor performance status, decompensated liver disease, or other major comorbidities are unlikely to benefit from this investigational therapy.
Why it matters
Potential benefit: If successful, the therapy could offer a targeted, off‑the‑shelf immunotherapy option that reduces antigen‑escape and improves control of GPC3/B7‑H3 positive advanced HCC.
How similar studies have performed: GPC3‑targeting cell therapies have shown early signals of activity in HCC, but dual‑target CAR‑NK approaches combining GPC3 and B7‑H3 remain largely experimental and not yet validated in late‑phase trials.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 18 to 75 years. * Histologically or cytologically confirmed HCC, or radiologically diagnosed HCC with mandatory tissue confirmation of target expression before enrollment. * Unresectable, locally advanced, or metastatic HCC not amenable to curative surgery, transplant, or further locoregional therapy; BCLC stage C, or stage B that is not suitable for or has progressed after locoregional therapy. * Disease progression on, intolerance to, or ineligibility for at least 1 prior standard systemic regimen. * Central pathology showing GPC3 positivity in \>=25% of viable tumor cells by IHC and B7-H3 positivity in \>=10% of tumor cells and/or tumor-associated stromal/vascular cells by IHC. * At least 1 measurable lesion by RECIST 1.1; intrahepatic lesions must be assessable by contrast-enhanced triphasic CT or MRI. * ECOG performance status 0 to 1. * Child-Pugh class A or stable Child-Pugh B7 without uncontrolled ascites or recent encephalopathy. * Estimated life expectancy \>=12 weeks. * Adequate organ function: WBC \>=2.5 x 10\^9/L; platelets \>=60 x 10\^9/L; hemoglobin \>=9 g/dL; serum albumin \>=30 g/L; creatinine clearance \>=40 mL/min; AST/ALT \<=5 x ULN; total bilirubin \<=2.5 x ULN; INR/prothrombin time within protocol-defined range. * If HBsAg positive or anti-HBc positive, HBV DNA must be \<200 IU/mL and the participant must be on appropriate antiviral therapy before lymphodepletion. Controlled HCV is allowed if per protocol. * Negative serum pregnancy test for participants of childbearing potential and agreement to effective contraception. * Ability to understand and sign informed consent. Exclusion Criteria: * Prior gene-modified cellular therapy (for example prior CAR-T, CAR-NK, or TCR-engineered therapy) within the protocol-defined washout period or with unresolved clinically significant toxicity. * Active, uncontrolled infection, including uncontrolled bacterial, viral, or fungal infection; uncontrolled HIV; active HBV or HCV with uncontrolled viral load; or active tuberculosis. * Known active CNS metastases or leptomeningeal disease requiring escalating steroids or urgent local intervention. * Liver transplant or other solid-organ transplant history, or current requirement for chronic immunosuppression. * Clinically significant ascites requiring frequent drainage, grade \>=2 hepatic encephalopathy within 4 weeks, or recent clinically significant variceal/GI bleeding. * Extensive liver replacement by tumor (for example \>=70%) or complete major portal vein/hepatic venous obstruction judged to create excessive treatment risk. * Major surgery, locoregional therapy, radiotherapy, or systemic anticancer therapy too close to lymphodepletion per protocol-defined washout period. * Active autoimmune disease requiring systemic immunosuppressive therapy, or chronic systemic corticosteroids above protocol threshold. * Clinically significant cardiovascular disease (recent myocardial infarction, unstable arrhythmia, uncontrolled heart failure), uncontrolled pulmonary disease, or other serious comorbidity that materially increases study risk. * Pregnant or breastfeeding. * Any other active malignancy that is progressing or requires current systemic treatment. * Any medical or psychiatric condition that, in the investigator's judgment, would compromise safety, protocol compliance, or interpretation of results.
Where this trial is running
Shenzhen, Guangdong
- Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: Seni S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.