Anti-Mesothelin CAR-T Cell Injection in Patients With Mesothelin-positive Advanced Malignant Solid Tumors

NCT07010523 | Recruiting

• 1 other identifier: [2024]TXB014
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-Mesothelin CAR-T cell injection in patients with Mesothelin-positive advanced malignant solid tumors.

Conditions

Mesothelin-positive Advanced Malignant Solid Tumors

Keywords

Anti-mesothelin CAR-T; Anti-MSLN CAR-T; Solid tumor

Outcome Measures

Primary Outcomes (4)

• Adverse Events (AEs)

  Incidence and severity of adverse events.

  2 years

• Serious Adverse Events (SAEs)

  Incidence and severity of serious adverse events.

  2 years

• Adverse Events of Special Interest (AESI)

  Incidence and severity of adverse event of special interest.

  2 years

• dentification of Maximum Tolerated Dose (MTD) & Incidence of Dose-limiting Toxicities (DLTs)

  Incidence and severity of dose-limiting toxicities (DLTs) following infusion of CAR-T cell injection, at each dose level tested in dose escalation phase.

  4 weeks after the CAR-T cells infusion

Secondary Outcomes (12)

• Objective Response Rate (ORR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Duration of Overall Response (DOR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

Anti-mesothelin CAR-T cells

EXPERIMENTAL

Anti-mesothelin CAR-T cells are autologous genetically modified T cells. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by injection.

Biological: Anti-mesothelin CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Anti-mesothelin CAR-T cells BIOLOGICAL

D0: 0.1×10\^6/Kg\~1.0×10\^6/Kg; cells will be infused intravenously.

Anti-mesothelin CAR-T cells

Fludarabine DRUG

D-7 to D-3: Fludarabine (25 mg/m\^2/day) will be administered intravenously for 5 days.

Anti-mesothelin CAR-T cells

Cyclophosphamide DRUG

D-7 to D-3: Cyclophosphamide (300 mg/m\^2/day) will be administered intravenously for 5 days.

Anti-mesothelin CAR-T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years old (including cut-off value), gender is not limited.
• Solid tumors that histological diagnosis of malignancy refractor to, or relapsing after standard therapy, including but not limited to mesothelioma, pancreatic cancer, biliary tract cancer, lung cancer, ovarian cancer, gastric cancer, bowel cancer, thymic carcinoma, esophageal cancer, breast cancer, endometrial cancer. Subjects have failed with standard treatment or cannot tolerate treatment recommended by clinical treatment guidelines form relevant international and domestic authoritative organization (Chinese Anti-Cancer Association(CACA), Chinese Society of Clinical Oncology(CSCO), National Health Commission, etc.)
• At least one measurable lesion according to RECIST v1.1.
• Mesothelin should be positive confirmed by Immunohistochemistry/Immunocytochemistry (IHC/ICC) in tumor tissue samples.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy ≥ 3 months.
• Adequate function defined as:
• Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients should not receive G-CSF support within 7 days before laboratory examination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients should not be transfused red cells within 7 days before the laboratory examination); Platelet count (PLT) ≥ 75 × 109/L (Patients should not receive transfusion support within 7 days before the laboratory examination).
• Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN); AST and ALT of patients with liver metastasis ≤ 5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with liver metastasis must ≤ 3.0 × ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 × ULN and Direct bilirubin (DBIL) ≤ 1.5 × ULN.
• Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are receiving therapeutic anticoagulants.).
• Renal functions: Serum creatinine (Cr) ≤ 1.5 × ULN; or Creatinine clearance rate (Ccr) ≥ 60 mL/min.
• Cardiac functions: Left ventricular ejection fraction (LVEF) \> 45%; Pulmonary function: Oxygen saturation (SpO2) \> 92%.
• Female participants of childbearing potential must undergo a pregnancy test and the results must be negative. Female participants of childbearing potential or male participants whose sex partner has childbearing potential must be willing to use effective methods of contraception from screening period to at least 1 year after infusion.
• Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.

You may not qualify if:

• Pregnant or lactating women.
• Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in peripheral blood is higher than the lower limit of detection. Patients who is hepatitis C virus (HCV) antibody positive and quantification of HCV RNA in peripheral blood is higher than the lower limit of detection. Patients with human immunodeficiency virus (HIV) antibody positive, or syphilis antibody positive.
• The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to CTCAE, except for hair loss and peripheral sensory nerve disorders.
• Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
• Patients have received anti-mesothelin CAR-T cell therapy.
• Patients who have history of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent; or plan to have major surgery within 12 weeks of cell therapy.
• Presence of known central nervous system metastases, but the following patients will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic progression within 4 weeks before apheresis and return of any neurologic symptoms to baseline), and with no need for corticosteroids or other treatment for brain metastases for ≥ 4 weeks.
• Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patients' ability to tolerate the treatments used in this study or significantly increase the risk of complications.
• Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);
• Congestive heart failure with New York Heart Association (NYHA) functional class \> 1;
• Clinically significant severe aortic stenosis and symptomatic mitral stenosis;
• Electrocardiogram QTc \> 450 msec or QTc \> 480 msec in patients with bundle-branch block;
• Uncontrolled clinically significant arrhythmia within 6 months prior to signing informed consent;
• Acute coronary syndrome (such as: unstable angina, myocardial infarction) within 6 months prior to signing informed consent;
• Drug-uncontrolled hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 100 mmHg) or pulmonary hypertension;

Sponsors & Collaborators

• Zhejiang University: lead
• UTC Therapeutics Inc.: collaborator

Study Sites (1)

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

MeSH Terms

Interventions

fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Weijia Fang, MD PhD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenyu Wang, MD PhD

CONTACT

+86 0571-87237587; wywang0815@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: June 8, 2025
• Study Start: October 15, 2024
• Primary Completion (Estimated): October 14, 2026
• Study Completion (Estimated): October 14, 2027
• Last Updated: June 8, 2025

Record last verified: 2025-02

Locations

CN (1)