Universal CAR-T therapy for metastatic colorectal cancer

A Clinical Study on the Safety and Efficacy of Universal CAR-T Cells (REVO-UWD-01) for Metastatic Colorectal Cancer

This study is testing a new type of CAR-T therapy for people with metastatic colorectal cancer to see if it is safe and effective in using modified T cells from healthy donors.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 30 (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: NCT06653010 on ClinicalTrials.gov

What this trial studies

This trial investigates the safety and efficacy of a novel universal CAR-T therapy targeting GCC in patients with metastatic colorectal cancer. It utilizes T cells from healthy donors that are modified to recognize GCC, aiming to improve treatment accessibility and reduce costs. Participants will undergo chemotherapy conditioning followed by the CAR-T cell infusion, with a focus on determining the maximum tolerated dose and monitoring for adverse events and treatment efficacy. The study will evaluate both short-term and long-term outcomes related to the treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with pathologically confirmed metastatic colorectal cancer expressing GCC and who have progressed after standard treatments.

Not a fit: Patients with colorectal cancer who have standard treatment options available or do not express GCC in their tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new, effective treatment option for patients with metastatic colorectal cancer who have limited or no standard treatment options.

How similar studies have performed: While CAR-T therapies have shown promise in other cancers, this specific approach using universal CAR-T cells for colorectal cancer is novel and has not been extensively tested.

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.

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 CRC; Metastatic Colorectal Cancer; Universal CAR-T cells; Allogeneic CAR-T therapy; Wondercel REVO U-CAR platform; REVO-UWD-01