Universal CAR-T Cells (REVO-UWD-03) for Advanced Hepatocellular Carcinoma and Lung Cancer

NCT ID: NCT06653023

Last Updated: 2026-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-23
• Study Completion Date: 2027-12-30

Brief Summary

This is an investigator initiated trial to assess the efficacy and safety of a GPC3-targeting CAR-T therapy (REVO-UWD-03) in the HCC and Lung Cancer. It also aims to explore the feasibility of using a novel universal CAR-T cell platform.

Detailed Description

The study will use T cells from healthy donors, modified using a novel universal CAR-T technology, to treat HCC and Lung Cancer patients. The antigen-binding site of the CAR molecule recognizes GPC3 as the target.

The main questions it aims to answer are: • What is the maximum tolerated dose (MTD) of GPC3-CAR-T therapy in universal CAR-T cell treatments? • What are the dose-limiting toxicities (DLT) and treatment-emergent adverse events (TEAE)? • What is the treatment efficacy, as measured by objective response rate (ORR) and progression-free survival (PFS)? Researchers will assess whether the universal CAR-T cells have good safety and efficacy in treating HCC or Lung cancer, while improving accessibility and lowering treatment costs. Participants will: • Receive universal GPC3-CAR-T cells through a 3+3 dose escalation scheme. • Undergo chemotherapy conditioning before CAR-T infusion. • Be monitored for adverse events, immune response, and disease progression.

The study will collect data on both short-term outcomes (within the first few months post-treatment) and long-term safety and efficacy.

Conditions

HCC - Hepatocellular Carcinoma; NSCLC (Advanced Non-small Cell Lung Cancer)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single dose injection of REVO-UWD-03

Dose escalation will be performed for the single dose injection of REVO-UWD-03 for treating HCC and NSCLC

Group Type: EXPERIMENTAL

Universal CAR-T cells injection for treating HCC and NSCLC

Intervention Type: BIOLOGICAL

Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after signing an informed consent form, followed by a one-time injection of one dose of universal REVO-UWD-03 CAR-T cells

MMF Immunosuppression

Intervention Type: DRUG

One day after the completion of fludarabine preconditioning (D-2), initiate oral mycophenolate sodium at a dose of 1440 mg twice daily (BID) for 15 consecutive days, or extend the duration appropriately based on CAR-T cell expansion status (discontinuation may occur at the end of CAR-T cell expansion or on the day of patient discharge). The maximum duration of administration must not exceed 30 days.

Interventions

Universal CAR-T cells injection for treating HCC and NSCLC

Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after signing an informed consent form, followed by a one-time injection of one dose of universal REVO-UWD-03 CAR-T cells

Intervention Type: BIOLOGICAL

MMF Immunosuppression

One day after the completion of fludarabine preconditioning (D-2), initiate oral mycophenolate sodium at a dose of 1440 mg twice daily (BID) for 15 consecutive days, or extend the duration appropriately based on CAR-T cell expansion status (discontinuation may occur at the end of CAR-T cell expansion or on the day of patient discharge). The maximum duration of administration must not exceed 30 days.

Intervention Type: DRUG

Other Intervention Names

REVO-UWD-03

Eligibility Criteria

Inclusion Criteria

1. Age: ≥18 years and ≤75 years;

2. Patients with histologically or cytologically confirmed, unresectable locally advanced or metastatic epithelial-origin hepatocellular carcinoma (HCC) who have failed standard therapy, or for whom no standard therapy is available, or who are unsuitable for standard therapy at this stage;

(1) Barcelona Clinic Liver Cancer (BCLC) stage B (not amenable to hepatic surgery and/or other local therapies, or disease progression after local therapy) or stage C; (2) Or China Liver Cancer (CNLC) stage IIb or III (not amenable to hepatic surgery and/or other local therapies, or disease progression after local therapy); 3. Immunohistochemistry (IHC) evaluation showing GPC3 expression ≥1+ in ≥50% of the tumor lesion area (randomly select at least 5 fields of view from tumor regions for evaluation; at least 5 unstained slides must be provided for assessment); 4. At least one measurable lesion: The measurable lesion must not have received prior radiotherapy, interventional therapy, or other local treatments (lesions in previously treated fields may be selected as target lesions if confirmed to have progressed); 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 6. Expected survival ≥90 days; 7. Adequate major organ function, meeting the following criteria:

1. Hematology: Absolute neutrophil count ≥1.5 × 10⁹/L; platelets ≥80 × 10⁹/L; hemoglobin ≥9.0 g/dL;

2. Liver function: Total bilirubin ≤5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN;

3. Renal function: Serum creatinine ≤5 × ULN or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m²;

4. Coagulation: Prothrombin time (PT) prolongation ≤4 seconds;

5. Cardiac function: Left ventricular ejection fraction (LVEF) >50%; 8. No hemorrhagic disorders or coagulopathy; 9. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment, and agree to use appropriate contraception from enrollment through 8 weeks after the last CAR-T administration (women who have undergone sterilization or been postmenopausal for at least 2 years are considered not of childbearing potential); 10. Voluntary participation in the study, signed informed consent, good compliance, and willingness to complete follow-up.

Exclusion Criteria

1. Pregnant or breastfeeding women;

2. Received chemotherapy, targeted therapy, other investigational drugs, or monoclonal antibody therapy within 14 days prior to cell collection;

3. Participated in another drug clinical trial within 4 weeks prior to study initiation;

4. Any of the following cardiovascular diseases or cardiovascular risk factors:

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wondercel Biotech (ShenZhen)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Jiangsu Cancer Hospital

Nanjing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Clinical Deveopment Director

Role: CONTACT

clinical@wondercel.com

+8618092039190

Facility Contacts

Yayun Zheng

Role: primary

clinical@wondercel.com

18092039190

Rong Yin, MD PhD

Role: primary

Other Identifiers

2024-REVO-UWD-03

Identifier Type: -

Identifier Source: org_study_id