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

NCT06653023 | Suspended Early Phase 1

• 1 other identifier: 2024-REVO-UWD-03
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Universal CAR-T cells; Allogeneic CAR-T therapy; Wondercel REVO U-CAR platform

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  The highest dose of universal GPC3-CAR-T cells that can be administered without causing unacceptable side effects, measured during the dose escalation phase.

  Within the first month post-infusion

• Dose-Limiting Toxicities (DLT)

  The incidence of treatment-related toxicities that prevent further dose escalation.

  Within the first month post-infusion.

• Treatment-Emergent Adverse Events (TEAE)

  The frequency and severity of adverse events that arise following the administration of universal GPC3-CAR-T cells.

  From the administration of UWD-03 CAR-T cells through six months post-infusion

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Measured at 3 and 6 months after treatment.

• Progression-Free Survival (PFS)

  From the start of treatment up to 5 years.

• Overall Survival (OS)

  From the start of treatment up to 5 years.

• Duration of Response (DOR)

  From the administration of UWD-03 CAR-T cells to a maximum follow-up period of five years.

Study Arms (1)

Single dose injection of REVO-UWD-03

EXPERIMENTAL

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

Biological: Universal CAR-T cells injection for treating HCC and NSCLC; Drug: MMF Immunosuppression

Interventions

Universal CAR-T cells injection for treating HCC and NSCLC 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

Also known as: REVO-UWD-03

Single dose injection of REVO-UWD-03

MMF Immunosuppression 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.

Single dose injection of REVO-UWD-03

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 years and ≤75 years;
• 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:
• Hematology: Absolute neutrophil count ≥1.5 × 10⁹/L; platelets ≥80 × 10⁹/L; hemoglobin ≥9.0 g/dL;
• Liver function: Total bilirubin ≤5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN;
• Renal function: Serum creatinine ≤5 × ULN or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m²;
• Coagulation: Prothrombin time (PT) prolongation ≤4 seconds;
• 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.

You may not qualify if:

• Pregnant or breastfeeding women;
• Received chemotherapy, targeted therapy, other investigational drugs, or monoclonal antibody therapy within 14 days prior to cell collection;
• Participated in another drug clinical trial within 4 weeks prior to study initiation;
• Any of the following cardiovascular diseases or cardiovascular risk factors:

Sponsors & Collaborators

• Wondercel Biotech (ShenZhen): lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 22, 2024
• Study Start: October 23, 2024
• Primary Completion (Estimated): October 20, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)