Advanced Hepatocellular Carcinoma (HCC)Phase 1/2DUET-HCCNCT07500220
Dual-Target GPC3/B7-H3 CAR-NK Cells for Advanced HCC
A Phase 1/2 study testing EB-G3B7-NK dual-target CAR-NK cells, Fludarabine and Cyclophosphamide in people with Advanced Hepatocellular Carcinoma (HCC) and Metastatic Liver Cancer, run by Beijing Biotech at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma (HCC), Metastatic Liver Cancer
- What is being tested?
- EB-G3B7-NK dual-target CAR-NK cells, Fludarabine and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 2 Mar 2026to 17 Mar 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036
Zhen J Peng, Phd, +86 13076790039, Zhen-Peng@beijing-biotech.com
About this study
Official title: 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.
Read the 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.
- Being tested
- EB-G3B7-NK dual-target CAR-NK cells, Fludarabine, Cyclophosphamide
- 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
- Medical subject headings
- Liver Neoplasms, Simpson-Golabi-Behmel syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EB-G3B7-NK dual-target CAR-NK cellsBiological
Also called Dual-target GPC3/B7-H3 CAR-NK; G3B7-NK; EB-G3B7-NK
Allogeneic donor-derived NK cells genetically modified to express a dual-target CAR recognizing GPC3 and B7-H3/CD276. Administered intravenously after lymphodepletion.
FludarabineDrug
Also called FC lymphodepletion
Lymphodepleting chemotherapy given before CAR-NK infusion.
CyclophosphamideDrug
Also called FC lymphodepletion
Lymphodepleting chemotherapy given before CAR-NK infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: EB-G3B7-NK dual-target CAR-NK cells; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities (DLTs)
Measured: 28 Days
Incidence, type, and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measured: 12 months
Secondary outcomes (5)
response rate (ORR) by RECIST 1.1 and mRECIST
Measured: 6 months
Disease control rate (DCR)
Measured: 6 months
Duration of response (DoR)
Measured: 12 months
Progression-free survival (PFS)
Measured: 12 months
Overall survival (OS)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2026
- Study start2 Mar 2026
- Primary completion14 Mar 2027 (estimated)
- Study completion17 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07500220
- Sponsor's protocol ID
- EB-HCC-DUET-101
- Acronym
- DUET-HCC
- Status last verified
- Mar 2026
- First submitted
- 17 Mar 2026
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No