Clinical trial NCT06653023: Universal CAR-T Cells (REVO-UWD-03) for Advanced Hepatocellular Carcinoma and Lung Cancer
Official title: A Clinical Study on the Safety and Efficacy of Universal CAR-T Cells (REVO-UWD-03) for Advanced Hepatocellular Carcinoma &Amp; Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
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
Lead sponsor: Wondercel Biotech (ShenZhen)
Sponsor class: INDUSTRY
First posted: 2024-10-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within the first month post-infusion
measure: Dose-Limiting Toxicities (DLT)
timeFrame: Within the first month post-infusion.
measure: Treatment-Emergent Adverse Events (TEAE)
timeFrame: From the administration of UWD-03 CAR-T cells through six months post-infusion
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Measured at 3 and 6 months after treatment.
measure: Progression-Free Survival (PFS)
timeFrame: From the start of treatment up to 5 years.
measure: Overall Survival (OS)
timeFrame: From the start of treatment up to 5 years.
measure: Duration of Response (DOR)
timeFrame: From the administration of UWD-03 CAR-T cells to a maximum follow-up period of five years.
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
Study officials:
References: