Universal CAR-T therapy for advanced liver and lung cancer

A Clinical Study on the Safety and Efficacy of Universal CAR-T Cells (REVO-UWD-03) for Advanced Hepatocellular Carcinoma &Amp; Lung Cancer

This study is testing a new CAR-T therapy that uses modified immune cells to see if it can help people with advanced liver and lung cancer feel better and live longer.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Wondercel Biotech (ShenZhen) (Industry-sponsored)
• Drugs / interventions: tocilizumab, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Xi'an, Shaanxi)
• Trial ID: NCT06653023 on ClinicalTrials.gov

What this trial studies

This trial evaluates the safety and efficacy of a novel GPC3-targeting CAR-T therapy, REVO-UWD-03, in patients with advanced hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC). It utilizes T cells from healthy donors modified through a universal CAR-T technology to target GPC3, a protein expressed in certain tumors. The study will determine the maximum tolerated dose, assess treatment-emergent adverse events, and measure treatment efficacy through objective response rates and progression-free survival. Participants will undergo chemotherapy conditioning before receiving the CAR-T cell infusion and will be monitored for both short-term and long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with unresectable advanced HCC or NSCLC who have failed standard treatments and express GPC3 in their tumors.

Not a fit: Patients with resectable tumors or those who do not express GPC3 in their tumor lesions may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced liver and lung cancers who have exhausted standard treatment options.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this specific approach using universal CAR-T cells for solid tumors is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Age: 18-80 years; Patients with histologically or cytologically confirmed, unresectable locally advanced or metastatic epithelial-derived malignant tumors who have failed standard treatments, have no available standard treatment options, or are unsuitable for standard treatments at the current stage, including but not limited to the following tumor types: non-small cell lung cancer or liver cancer; Immunohistochemistry (IHC) assessment shows GPC3 expression in ≥50% of the tumor lesion area with ≥1+ staining (assessment should be conducted on at least five randomly selected tumor regions, and at least five blank slides should be provided for evaluation); At least one measurable lesion; Estimated survival time of ≥90 days;

Normal major organ functions, meeting the following criteria: a. Absolute neutrophil count ≥1.5 x 10\^9/L; b. Platelet count ≥80 x 10\^9/L; c. Hemoglobin ≥9 g/dL; d. Liver function:

Total bilirubin ≤1.5 times the upper limit of normal (ULN), for Gilbert's syndrome patients, bilirubin ≤2.0 times ULN; Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 times ULN; e. International Normalized Ratio (INR) \<1.3 (for patients on anticoagulant therapy, INR \<3 is acceptable); f. Serum creatinine ≤1.5 mg/dL (132.6 μmol/L) or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m²; g. Left ventricular ejection fraction \>50%; No hemorrhagic disorders or coagulation dysfunctions; Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before enrollment and be willing to use appropriate contraception during the study and for 8 weeks after the last CAR-T administration (women who have undergone sterilization or are postmenopausal for at least 2 years are considered not to have childbearing potential); The subject voluntarily agrees to participate in the study, signs the informed consent form, and demonstrates good compliance for follow-up.

Exclusion Criteria:

* Pregnant or breastfeeding women; Receipt of chemotherapy, targeted therapy, other experimental drugs, or monoclonal antibody treatment within 14 days before enrollment for cell collection; Participation in other drug clinical trials within 4 weeks prior to the start of the study; Presence of any of the following cardiovascular or cerebrovascular diseases or risk factors: a. Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, grade 3 or 4 heart failure (according to NYHA classification), symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other serious cardiovascular diseases within 6 months prior to enrollment; b. History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy; c. Any events of disseminated intravascular coagulation (DIC), peripheral arterial thromboembolism, pulmonary embolism, or other severe thromboembolic events within 3 months prior to enrollment; d. Presence of aortic aneurysm, aortic dissection, or other major vascular diseases requiring surgery within 6 months prior to enrollment or posing a life-threatening risk; e. QTcF interval \>480 ms; f. Left ventricular ejection fraction (LVEF) \<50% on ECHO; Long-term unhealed wounds or fractures; History of substance abuse or psychiatric disorders that cannot be controlled or a history of mental illness; Uncontrolled or active fungal, bacterial, viral, or other infections; Toxicities from previous anti-tumor treatments not yet recovered to grade ≤1 or to the levels specified in the inclusion/exclusion criteria; Known HIV infection; active syphilis infection; or active hepatitis B (HBsAg positive, and HBV-DNA ≥500 IU/mL or above the detection limit, whichever is higher) or hepatitis C (HCV antibody positive, and HCV-RNA above the detection limit); Uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage despite appropriate intervention; History of severe allergic reactions to key study medications (including fludarabine, cyclophosphamide, mesna, tocilizumab, or anti-infection drugs used during the preconditioning phase); Active autoimmune diseases requiring systemic treatment within two years (including but not limited to autoimmune hepatitis, uveitis, colitis, hypophysitis, vasculitis, nephritis, or hyperthyroidism); hormone replacement therapy, such as thyroid hormones, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency, is not considered systemic treatment; Female subjects unwilling to use contraception from the time of signing the consent form until 6 months after completion of CAR-T cell infusion; Patients with meningeal metastasis, brainstem metastasis, spinal cord metastasis and/or compression, active or untreated CNS metastasis; History of interstitial lung disease (ILD) or non-infectious pneumonia requiring steroid treatment; Clinically significant lung damage due to pulmonary complications, including but not limited to any underlying lung disease (e.g., pulmonary embolism, severe asthma, or severe chronic obstructive pulmonary disease (COPD) within 3 months prior to enrollment), or any autoimmune, connective tissue, or inflammatory disease affecting the lungs (e.g., rheumatoid arthritis, sarcoidosis), or prior complete lung resection; Any condition that the investigator believes may interfere with drug evaluation, the safety of the subject, or study outcomes, or any condition deemed inappropriate by the investigator for study participation.

Where this trial is running

Xi'an, Shaanxi

• First Affiliated Hospital of Xi'an Jiaotong University — Xi'an, Shaanxi, China (Recruiting)

Study contacts

• Study coordinator: Clinical Deveopment Director

Conditions HCC - Hepatocellular Carcinoma; NSCLC; Universal CAR-T cells; Allogeneic CAR-T therapy; Wondercel REVO U-CAR platform