Dual-Target GPC3/B7-H3 CAR-NK Cells for Advanced HCC

NCT07500220 | Recruiting Phase 1 DMC

• 1 other identifier: EB-HCC-DUET-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

open-label trial of an allogeneic dual-target CAR-NK product directed against GPC3 and B7-H3 for adults with advanced hepatocellular carcinoma. The design intentionally uses GPC3 as the primary target anchor because GPC3 is the dominant HCC cell-therapy antigen in current clinical development, while adding B7-H3 to reduce antigen escape and to broaden coverage across tumor and tumor-microenvironment compartments. The study first evaluates safety and dose-limiting toxicities, then expands at the recommended phase 2 dose.

Conditions

Advanced Hepatocellular Carcinoma (HCC); Metastatic Liver Cancer

Keywords

HCC; liver cancer; epatocellular carcinoma; GPC3; glypican-3; B7-H3; CD276; CAR-NK; dual-target; NK cell therapy; adoptive cell therapy; cell therapy; immunotherapy; allogeneic

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  28 Days

• Incidence, type, and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

  12 months

Secondary Outcomes (5)

• response rate (ORR) by RECIST 1.1 and mRECIST

  6 months

• Disease control rate (DCR)

  6 months

• Duration of response (DoR)

  12 months

• Progression-free survival (PFS)

  12 months

• Overall survival (OS)

  24 months

Study Arms (1)

EB-G3B7-NK dual-target CAR-NK cells

EXPERIMENTAL

Adults with biomarker-confirmed advanced HCC receive fludarabine/cyclophosphamide lymphodepletion followed by allogeneic dual-target GPC3/B7-H3 CAR-NK cells at an assigned dose level in Phase 1 or at the RP2D in Phase 2.

Biological: EB-G3B7-NK dual-target CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

EB-G3B7-NK dual-target CAR-NK cells BIOLOGICAL

Allogeneic donor-derived NK cells genetically modified to express a dual-target CAR recognizing GPC3 and B7-H3/CD276. Administered intravenously after lymphodepletion.

Also known as: Dual-target GPC3/B7-H3 CAR-NK; G3B7-NK; EB-G3B7-NK

EB-G3B7-NK dual-target CAR-NK cells

Fludarabine DRUG

Lymphodepleting chemotherapy given before CAR-NK infusion.

Also known as: FC lymphodepletion

EB-G3B7-NK dual-target CAR-NK cells

Cyclophosphamide DRUG

Lymphodepleting chemotherapy given before CAR-NK infusion.

Also known as: FC lymphodepletion

EB-G3B7-NK dual-target CAR-NK cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Liver Neoplasms; Simpson-Golabi-Behmel syndrome

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Masking is not used because this is an early-phase cell-therapy study in which real-time safety management, product-specific monitoring, and dose-escalation decisions require investigators and treating teams to know the intervention
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, nonrandomized, biomarker-confirmed, single-arm study with a Phase 1 dose-escalation segment (3+3 design across 3 dose levels) followed by a Phase 2 dose-expansion cohort at the RP2D. All enrolled participants receive lymphodepleting chemotherapy followed by dual-target GPC3/B7-H3 CAR-NK cells. Responses are assessed by RECIST 1.1 and mRECIST for HCC.

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: March 30, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

CN (1)