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

March 24, 2026 updated by: Beijing Biotech

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma (HCC) remains a high-mortality solid tumor, and many patients progress after or are not candidates for surgery, transplant, locoregional therapy, immune-checkpoint inhibitors, or tyrosine-kinase inhibitors.

Among HCC-associated cell-surface targets, GPC3 has the strongest disease-specific cell-therapy track record and is widely used as the anchor antigen in HCC CAR-T programs. However, not all HCCs express GPC3 uniformly, and loss or low-density expression may contribute to resistance and escape. B7-H3 is an attractive secondary co-target because it is frequently expressed in HCC tumor and stromal/vascular compartments, is associated with immune suppression and aggressive biology, and may complement GPC3 when antigen heterogeneity is present.

The investigational product in this draft is an allogeneic donor-derived peripheral blood NK-cell product genetically engineered to express a dual-target CAR recognizing GPC3 and B7-H3. To keep this example realistic and conservative, the core registration fields below assume a standard dual-target CAR-NK product plus fludarabine/cyclophosphamide lymphodepletion. If the sponsor later prefers an armored platform , those features can be added in a subsequent protocol version or IND-enabling package.

The study is structured as a phase 1/2 single-group trial. Phase 1 uses dose-escalation to determine safety, the recommended phase 2 dose (RP2D), and feasibility. Phase 2 expands at the RP2D to estimate preliminary anti-tumor activity. Participants receive lymphodepleting chemotherapy before CAR-NK infusion, then undergo protocol-defined safety monitoring, serial imaging, and translational assessments including CAR-NK persistence, serum AFP, cytokine profiling, and ctDNA dynamics.

Because B7-H3 can also be detected at low levels in some normal tissues, the trial is intentionally conservative: it uses central biomarker confirmation, stepwise dose escalation, strict liver function eligibility, and close monitoring for infusion reactions, cytokine-release syndrome, immune effector cell-associated neurotoxicity, hepatotoxicity, cytopenias, infection, and any evidence of off-tumor toxicity.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EB-G3B7-NK dual-target CAR-NK cells
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
Allogeneic donor-derived NK cells genetically modified to express a dual-target CAR recognizing GPC3 and B7-H3/CD276. Administered intravenously after lymphodepletion.
Other Names:
  • Dual-target GPC3/B7-H3 CAR-NK; G3B7-NK; EB-G3B7-NK
Drug: Fludarabine
Lymphodepleting chemotherapy given before CAR-NK infusion.
Other Names:
  • FC lymphodepletion
Drug: Cyclophosphamide
Lymphodepleting chemotherapy given before CAR-NK infusion.
Other Names:
  • FC lymphodepletion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 Days
28 Days
Incidence, type, and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 24 months
24 months
Progression-free survival (PFS)
Time Frame: 12 months
12 months
Disease control rate (DCR)
Time Frame: 6 months
6 months
response rate (ORR) by RECIST 1.1 and mRECIST
Time Frame: 6 months
6 months
Duration of response (DoR)
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2026

Primary Completion (Estimated)

March 14, 2027

Study Completion (Estimated)

March 17, 2028

Study Registration Dates

First Submitted

March 17, 2026

First Submitted That Met QC Criteria

March 24, 2026

First Posted (Actual)

March 30, 2026

Study Record Updates

Last Update Posted (Actual)

March 30, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-HCC-DUET-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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