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Efficacy and Safety of MSLN CAR-T in Advanced Malignant Tumors | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Efficacy and Safety of MSLN CAR-T in Advanced Malignant Tumors

NCT07399769•Shenzhen University General Hospital

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.

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

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;
+1 more criteria

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;
+10 more criteria

Locations (1)

Shenzhen University General Hospital

Shenzhen, Other (Non U.s.), China

Key Dates

Start Date

January 1, 2024

Primary Completion Date

January 30, 2027

Completion Date

January 30, 2027

Last Updated

February 10, 2026

Enrollment

ESTIMATED participants

Conditions

Advanced Solid Malignant Tumors (With Positive Expression of MSLN in Tumor Tissue)

Interventions

CAR-T

COMBINATION_PRODUCT

Contacts

Guocheng Zhong

CONTACT

0755-21839999 m18716354367@163.com