MSLN CAR-T for advanced malignant tumors

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

This trial will test whether a single infusion of MSLN-targeted CAR-T cells is safe and can shrink tumors in adults (18–75) with stage III/IV solid cancers that express mesothelin.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shenzhen University General Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, Cyclophosphamide, Fludarabine
• Locations: 1 site (Shenzhen, Other (Non U.s.))
• Trial ID: NCT07399769 on ClinicalTrials.gov

What this trial studies

This Phase 1/2, single-site interventional study enrolls 20 adults with unresectable, locally advanced, recurrent, or metastatic solid tumors that are positive for mesothelin (MSLN) by immunohistochemistry. Participants receive lymphodepleting chemotherapy (fludarabine + cyclophosphamide on Days −5 to −3) followed 72 hours later by a single intravenous infusion of MSLN CAR-T cells at 0.5–2 × 10^6 CAR-T cells/kg. The primary endpoint is incidence and severity of treatment-emergent adverse events within 30 days of infusion; secondary endpoints include objective response rate at 8 weeks and 6-month overall and progression-free survival. The study will also measure in vivo expansion and persistence of the infused CAR-T cells and explore correlations with clinical outcomes.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed stage III or IV unresectable, recurrent, or metastatic solid tumors that are measurable by RECIST v1.1 and show positive MSLN expression by IHC who have progressed on or are intolerant of standard first-line therapy and are not candidates for curative treatment.

Not a fit: Patients whose tumors do not express MSLN, who have earlier-stage disease amenable to curative therapy, or who remain eligible for standard curative options are unlikely to benefit from this investigational CAR-T approach.

Why it matters

Potential benefit: If successful, MSLN-targeted CAR-T could offer a new targeted treatment that shrinks tumors and potentially prolongs survival for patients with mesothelin-positive advanced solid cancers.

How similar studies have performed: Other early-phase mesothelin-targeted CAR-T and mesothelin-directed therapies have shown occasional signals of activity in small trials, but definitive, widely replicated efficacy has not yet been established.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Other (Non U.s.)

• Shenzhen University General Hospital — Shenzhen, Other (Non U.s.), China (Recruiting)

Study contacts

• Principal investigator: Li Yu — Shenzhen University General Hospital
• Study coordinator: Guocheng Zhong

Conditions Advanced Solid Malignant Tumors