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

Обзор

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.

Подробное описание

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.

Вмешательства

• Комбинированный продукт 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.

Первичные конечные точки

• TRAEs [Срок оценки: From date of initial treatment to the 30 days after treatment]

Вторичные конечные точки (1)

• Disease-related clinical responses [Срок оценки: From date of enrollment until the date of clinical responses,up to 2 years]

Критерии участия

Критерии включения

• Aged 18-75 years (≥18 and ≤75 years), either sex;
• The subject voluntarily participates in the study and provides written informed consent signed by the subject or his/her legally authorized representative;
• 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;
• Presence of measurable and evaluable lesions according to RECIST v1.1;
• Positive MSLN expression in tumor tissue confirmed by immunohistochemistry (IHC);
• The subject must have received standard first-line therapy and has experienced disease progression or is intolerant to such therapy;
• The subject is not suitable for curative treatment modalities such as definitive chemoradiotherapy and/or surgery/immune checkpoint inhibitors, or refuses surgical resection;
• No antibody-based therapy administered within 2 weeks prior to cell therapy;
• ECOG performance status 0-2;
• No contraindications to peripheral blood leukapheresis;
• Estimated life expectancy ≥ 3 months.

Критерии исключения

• History of allergy to any component of the cell product;
• 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;
• 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;
• NYHA class III or IV heart failure per the New York Heart Association functional classification, or left ventricular ejection fraction (LVEF) < 50% on echocardiography;
• Abnormal pulmonary function with oxygen saturation (SpO₂) < 92% on room air;
• History of myocardial infarction, coronary angioplasty or stenting, unstable angina, or other clinically significant severe cardiac disease within 12 months prior to enrollment;
• Grade 3 hypertension with poor blood pressure control despite medical treatment;
• History of traumatic brain injury, disturbance of consciousness, epilepsy, or severe cerebral ischemic or hemorrhagic disease;
• Presence of autoimmune disease, immunodeficiency, or other conditions requiring immunosuppressive therapy;
• Presence of uncontrolled active infection;
• Prior treatment with any CAR-T cell product or other genetically modified T-cell therapy;
• Receipt of a live vaccine within 4 weeks prior to enrollment;
• Positive test results for HIV, HBV, HCV, and TPPA/RPR, and/or HBV carriers;
• History of alcohol abuse, illicit drug use, or psychiatric disorders;
• Participation in any other clinical study within 3 months prior to enrollment;
• Female subjects meeting any of the following:

• pregnant or breastfeeding; or
• planning pregnancy during the study period; or
• of childbearing potential and unable/unwilling to use effective contraception;
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Организация здравоохранения

Центры проведения

Китай · 1 центр

• Shenzhen University General Hospital — Шэньчжэнь

Идентификаторы

NCT: NCT07399769 · 112

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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