Trial Title:
Universal CAR-T Cells (REVO-UWD-03) for Advanced Hepatocellular Carcinoma and Lung Cancer
NCT ID:
NCT06653023
Condition:
HCC - Hepatocellular Carcinoma
NSCLC (advanced Non-small Cell Lung Cancer)
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Carcinoma, Hepatocellular
Conditions: Keywords:
Universal CAR-T cells
Allogeneic CAR-T therapy
Wondercel REVO U-CAR platform
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Universal CAR-T cells injection for treating HCC and NSCLC
Description:
A novel universal CAR-T platform to treat cancer patients
Arm group label:
Single dose injection of REVO-UWD-03
Other name:
REVO-UWD-03
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The first affiliated hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710049
Country:
China
Status:
Recruiting
Contact:
Last name:
Yu Yao, M.D.,PhD.
Phone:
+8618991232380
Email:
yaoyu@mail.xjtu.edu.cn
Contact backup:
Last name:
Yu Yao, M.D. Ph.D.
Start date:
October 23, 2024
Completion date:
December 30, 2027
Lead sponsor:
Agency:
Wondercel Biotech (ShenZhen)
Agency class:
Industry
Source:
Wondercel Biotech (ShenZhen)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06653023
