Trial Title:
Universal CAR-T Cells (REVO-UWD-01) for Metastatic Colorectal Cancer
NCT ID:
NCT06653010
Condition:
CRC (colorectal Cancer)
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Universal CAR-T cells
Allogeneic CAR-T therapy
Wondercel REVO U-CAR platform
REVO-UWD-01
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 mCRC
Description:
A novel universal CAR-T platform to treat cancer patients
Arm group label:
Single dose injection of REVO-UWD-01
Other name:
Allogeneic CAR-T cells (REVO-UWD-01)
Summary:
This is an investigator initiated trial to assess the efficacy and safety of a
GCC-targeting CAR-T therapy (REVO-UWD-01) in the metastatic colorectal 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 metastatic colorectal cancer patients. The antigen-binding site of
the CAR molecule recognizes GCC as the target.
The main questions it aims to answer are:
- What is the maximum tolerated dose (MTD) of GCC-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's efficacy, as measured by objective response rate
(ORR) and progression-free survival (PFS)? Researchers will assess whether universal
CAR-T cells have good safety and efficacy in treating colorectal cancer, while
improving accessibility and lowering treatment costs.
Participants will:
- Receive universal GCC-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:
1. Age: 18-80 years old;
2. Pathologically confirmed colorectal cancer with liver metastases;
3. Immunohistochemistry (IHC) assessment shows GCC expression in tumor lesions of ≥1+
in more than 50% of the region (evaluation is performed by randomly selecting at
least five tumor areas, and at least five unstained slides must be provided for
assessment);
4. At least one measurable lesion;
5. Patients with colorectal cancer who have no standard treatment available, have
progressed after third-line therapy, or are intolerant to third-line treatment;
6. Expected survival time of ≥90 days;
7. Normal function of major organs, as defined by the following criteria:
1. Absolute neutrophil count (ANC) ≥1.5 x 10^9/L;
2. Platelets ≥80 x 10^9/L;
3. Hemoglobin ≥9 g/dL;
4. Liver function:
Total bilirubin ≤1.5 times the upper limit of normal (ULN), with subjects with
Gilbert's syndrome having bilirubin ≤2.0 times ULN; Aspartate aminotransferase
(AST) and alanine aminotransferase (ALT) ≤1.5 times ULN (≤3.0 times ULN if
liver metastases are present);
5. International normalized ratio (INR) <1.3; if the subject is receiving
anticoagulant therapy, INR <3 is required;
6. Serum creatinine ≤1.5 mg/dL (132.6 µmol/L) or estimated glomerular filtration
rate (eGFR) ≥50 mL/min/1.73 m²;
7. Left ventricular ejection fraction (LVEF) >50%;
8. No bleeding disorders or coagulation dysfunction;
9. Women of childbearing potential must undergo a pregnancy test (serum or urine)
within 7 days prior to enrollment, with a negative result, and must be willing to
use appropriate contraception during the trial and for 8 weeks after the last CAR-T
administration (women who have undergone sterilization or have been postmenopausal
for at least 2 years are considered non-childbearing);
10. Subjects must voluntarily participate in the study, sign the informed consent form,
have good compliance, and be willing to cooperate with follow-up.
Exclusion Criteria:
1. Pregnant or breastfeeding women;
2. Receipt of chemotherapy, targeted therapy, monoclonal antibody therapy, or
traditional Chinese anti-tumor medicine within 14 days prior to cell collection for
enrollment;
3. Participation in another clinical drug trial within 4 weeks before the start of the
study;
4. Presence of any of the following cardiovascular diseases or risk factors:
1. Myocardial infarction, unstable angina, acute or persistent myocardial
ischemia, Grade 3 or 4 heart failure (according to NYHA classification), severe
symptomatic or poorly controlled arrhythmia, cerebrovascular accident,
transient ischemic attack, or other serious cardiovascular diseases within 6
months prior to enrollment;
2. History of myocarditis, primary cardiomyopathy, or specific cardiomyopathy;
3. Disseminated intravascular coagulation (DIC), peripheral arterial thrombosis,
pulmonary embolism, or other severe thromboembolic events within 3 months prior
to enrollment;
4. Aortic aneurysm, aortic dissection, or other life-threatening vascular diseases
requiring surgery within 6 months prior to enrollment;
5. QTcF interval >480 ms;
6. Left ventricular ejection fraction (LVEF) <50% as shown by echocardiography
(ECHO);
5. Long-standing unhealed wounds or fractures;
6. Presence of bleeding disorders or coagulation dysfunction;
7. History of substance abuse involving psychiatric medications, or a history of mental
illness that cannot be controlled;
8. Uncontrolled or active fungal, bacterial, viral, or other infections;
9. Previous anti-tumor treatment toxicity that has not recovered to ≤ Grade 1 or to the
levels specified in the inclusion criteria;
10. Known HIV infection; active syphilis infection; or active hepatitis B
(HBsAg-positive, and HBV-DNA ≥500 IU/mL or above the lower limit of detection,
whichever is higher) or hepatitis C virus infection (HCV antibody-positive, and
HCV-RNA above the lower limit of detection);
11. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage despite appropriate intervention;
12. History of severe allergic reactions to the main therapeutic drugs in this study
(including fludarabine, cyclophosphamide, mesna, tocilizumab, and anti-infective
drugs used during preconditioning);
13. Patients with active autoimmune diseases requiring systemic treatment within the
past two years (including but not limited to autoimmune hepatitis, uveitis,
enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, etc.); hormone
replacement therapy, such as thyroid hormone, insulin, or physiological
corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not
considered systemic treatment;
14. Female subjects unwilling to use contraception from the time of signing the consent
form until 6 months after CAR-T cell infusion;
15. Patients with meningeal, brainstem, spinal cord metastases, and/or compression, or
active or untreated central nervous system (CNS) metastases;
16. History of interstitial lung disease (ILD) or non-infectious pneumonia requiring
corticosteroid treatment;
17. Clinically severe lung damage caused by pulmonary complications, including but not
limited to any underlying lung disease (e.g., pulmonary embolism within 3 months
prior to enrollment, severe asthma, severe chronic obstructive pulmonary disease) or
any autoimmune, connective tissue, or inflammatory disease affecting the lungs
(e.g., rheumatoid arthritis, sarcoidosis, etc.), or previous total lung resection;
18. Any condition that the investigator believes could interfere with drug evaluation,
compromise the subject's safety, or affect the study results, or any condition that
the investigator deems unsuitable for participation in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Nanjing Medical University Affiliated Cancer Hospital
Address:
City:
Nanjing
Zip:
210000
Country:
China
Status:
Recruiting
Contact:
Last name:
Rong Yin, M.D.,PhD.
Phone:
86-18305185629
Email:
rong_yin@njmu.edu.cn
Facility:
Name:
The first affiliated hospital of Xi'an Jiaotong University
Address:
City:
Xian
Zip:
710049
Country:
China
Status:
Recruiting
Contact:
Last name:
Yu Yao, M.D.,PhD.
Phone:
86-18991232380
Email:
yaoyu@mail.xjtu.edu.cn
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/NCT06653010
