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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Malignant Tumors (With Positive Expression of MSLN in Tumor Tissue)
• Intervention / Treatment: Combination product: CAR-T

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Guocheng Zhong; Phone Number: 0755-21839999; Email: m18716354367@163.com

Study Locations

• China
  • Other (Non U.s.)
    • Shenzhen, Other (Non U.s.), China, 518055
      • Recruiting
      • Shenzhen University General Hospital
      • Contact: Guocheng Zhong; Phone Number: 17358524782; Email: m18716354367@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CART group; 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.	Combination product: CAR-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TRAEs	Adverse events during treatment	From date of initial treatment to the 30 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-related clinical responses	Disease-related clinical responses include CR/PR/SD/PD	From date of enrollment until the date of clinical responses,up to 2 years

Collaborators and Investigators

• Sponsor: Shenzhen University General Hospital
• Investigators: Principal Investigator: Li Yu, Shenzhen University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2027

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No