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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 2, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 14, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 17, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 30, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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