Advanced Solid Malignant Tumors (With Positive Expression of MSLN in Tumor Tissue)
Conditions
Brief summary
1. Study Title: Efficacy and safety of MSLN CAR-T in advanced malignant tumors 2. Study Objectives: Primary: To evaluate the safety and tolerability of MSLN-targeted CAR-T cell therapy in patients with stage III/IV advanced malignant tumors. Secondary: To preliminarily evaluate the efficacy of MSLN-targeted CAR-T cell therapy in this patient population. Exploratory: To assess in vivo expansion and persistence of infused MSLN-targeted CAR-T cells and explore correlations with clinical outcomes. 3. Participant Intervention: Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned MSLN CAR-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.
Detailed description
Detailed Description: This is a prospective, interventional Phase I/II clinical study designed to evaluate the safety and efficacy of MSLN-targeted CAR-T cell therapy in patients with advanced malignant tumors. A total of 20 patients aged 18-75 years with unresectable, locally advanced, recurrent, or metastatic solid malignancies will be enrolled. All patients must have histopathologically confirmed disease and positive MSLN expression in tumor tissue. MSLN CAR-T cells will be administered as a single intravenous infusion at a total dose of 0.5-2 × 10\^6 CAR-T cells/kg. Eligible subjects (N=20) will be assigned by the investigator to receive MSLN CAR-T cell infusion. Endpoints: * Primary Endpoint: o Incidence and severity of treatment-emergent adverse events (TEAEs) within 30 days after MSLN CAR-T cell infusion. * Secondary Endpoints: * Objective response rate (ORR = CR + PR) assessed within 8 weeks after infusion; * Overall survival (OS) and progression-free survival (PFS) at 6 months; * In vivo expansion and persistence kinetics of infused CAR-T cells.
Interventions
COMBINATION_PRODUCTCAR-T
Participants will receive lymphodepleting chemotherapy (FC regimen: Fludarabine + Cyclophosphamide) on Days -5, -4, and -3 relative to the planned MSLN CAR-T cell infusion. The CAR-T cell infusion will be administered 72 hours after the completion of the FC chemotherapy.
Sponsors
Shenzhen University General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18-75 years (≥18 and ≤75 years), either sex; 2. The subject voluntarily participates in the study and provides written informed consent signed by the subject or his/her legally authorized representative; 3. Histopathologically confirmed unresectable, locally advanced, recurrent, or metastatic solid malignant tumor; according to the AJCC TNM staging system (8th edition, 2017), subjects diagnosed with stage III or stage IV solid malignant tumors; 4. Presence of measurable and evaluable lesions according to RECIST v1.1; 5. Positive MSLN expression in tumor tissue confirmed by immunohistochemistry (IHC); 6. The subject must have received standard first-line therapy and has experienced disease progression or is intolerant to such therapy; 7. The subject is not suitable for curative treatment modalities such as definitive chemoradiotherapy and/or surgery/immune checkpoint inhibitors, or refuses surgical resection; 8. No antibody-based therapy administered within 2 weeks prior to cell therapy; 9. ECOG performance status 0-2; 10. No contraindications to peripheral blood leukapheresis; 11. Estimated life expectancy ≥ 3 months.
Exclusion criteria
1. History of allergy to any component of the cell product; 2. Any of the following hematologic abnormalities on complete blood count (CBC): WBC ≤ 1 × 10\^9/L, absolute neutrophil count (ANC) ≤ 0.5 × 10\^9/L, absolute lymphocyte count (ALC) ≤ 0.5 × 10\^9/L, or platelets (PLT) ≤ 25 × 10\^9/L; 3. Any of the following laboratory abnormalities, including but not limited to: serum total bilirubin ≥ 1.5 mg/dL; serum ALT or AST \> 2.5 × ULN; serum creatinine ≥ 2.0 mg/dL; 4. NYHA class III or IV heart failure per the New York Heart Association functional classification, or left ventricular ejection fraction (LVEF) \< 50% on echocardiography; 5. Abnormal pulmonary function with oxygen saturation (SpO₂) \< 92% on room air; 6. History of myocardial infarction, coronary angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment; 7. Grade 3 hypertension with poor blood pressure control despite medical treatment; 8. History of traumatic brain injury, disturbance of consciousness, epilepsy, or severe cerebral ischemic or hemorrhagic disease; 9. Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy; 10. Presence of uncontrolled active infection; 11. Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy; 12. Receipt of a live vaccine within 4 weeks prior to enrollment; 13. Positive test results for HIV, HBV, HCV, and TPPA/RPR, and/or HBV carriers; 14. History of alcohol abuse, illicit drug use, or psychiatric disorders; 15. Participation in any other clinical study within 3 months prior to enrollment; 16. Female subjects meeting any of the following: 1. pregnant or breastfeeding; or 2. planning pregnancy during the study period; or 3. of childbearing potential and unable/unwilling to use effective contraception; 17. Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TRAEs | From date of initial treatment to the 30 days after treatment | Adverse events during treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-related clinical responses | From date of enrollment until the date of clinical responses,up to 2 years | Disease-related clinical responses include CR/PR/SD/PD |
Countries
China
Contacts
CONTACTGuocheng Zhong
PRINCIPAL_INVESTIGATORLi Yu
Shenzhen University General Hospital
Outcome results
None listed