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Mesothelin-positive Advanced Malignant Solid TumorsNCT07010523

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

A study testing Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide in people with Mesothelin-positive Advanced Malignant Solid Tumors, run by First Affiliated Hospital of Zhejiang University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteChina
Study dates
15 Oct 2024to 14 Oct 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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.
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  • 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.

Who cannot join

  • 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.
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  • 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;
  • Cerebrovascular accident occurred within 6 months prior to signing informed consent, including transient ischemic attack (TIA), cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage;
  • A history of active, chronic, or recurrent (within 1 year prior to signing informed consent) severe autoimmune disease or immune-mediated disease requiring steroids or other immunosuppressive therapy, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis. Exceptions: hypothyroidism that can be controlled only by hormone replacement therapy, skin diseases (such as: vitiligo, psoriasis) that do not require systemic treatment, coeliac disease that has been controlled;
  • Any form of primary or secondary immunodeficiency, such as severe combined immunodeficiency (SCID);
  • Possibility of bleeding from esophageal or gastric varices evaluated by the investigator.
  • History of severe systemic hypersensitivity reaction to the drugs/ingredients [fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular dextran, human serum albumin (HSA), etc.] used in this study.
  • Patients have received attenuated vaccine within 4 weeks prior to signing informed consent.
  • Patients have received other clinical trials within 4 weeks prior to signing informed consent.
  • History of another malignancy tumor within the previous five years, except for adequately treated non-melanoma skin cancer, carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
  • History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator, including but not limited to epilepsy, schizophrenia, dementia, drug and alcohol addictions.
  • For any other reasons, the patients are believed not suitable for participation in this study by investigators.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Wenyu Wang, MD PhD contact

+86 0571-87237587

wywang0815@zju.edu.cn

China1 site, 1 recruiting

  • The First Affiliated Hospital Zhejiang University School of Medicine

    Hangzhou

    Wenyu Wang, MD PhD, +86 0571-87237587, wywang0815@zju.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Exploratory 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

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.

Read the detailed description

In this study, patients with advanced malignant solid tumors with positive MSLN expression will be included. All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by Anti-MSLN CAR-T cell injection.

The dose escalation phase will determine the maximum tolerated dose (MTD) of Anti-MSLN CAR-T cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of Anti-MSLNCAR-T cell injection, and establish recommended phase 2 dose (RP2D).

Being tested
Anti-mesothelin CAR-T cells, Fludarabine, Cyclophosphamide
Keywords
Anti-mesothelin CAR-T, Anti-MSLN CAR-T, Solid tumor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-mesothelin CAR-T cellsBiological

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

  • FludarabineDrug

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

  • CyclophosphamideDrug

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

Study groups in NCT07010523
Study groupRoleWhat they receive
Anti-mesothelin CAR-T cellsExperimentalAnti-mesothelin CAR-T cells are autologous genetically modified T cells. A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by injection.
Receives: Biological: Anti-mesothelin CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse Events (AEs)

    Incidence and severity of adverse events.

    Measured: 2 years

  2. Serious Adverse Events (SAEs)

    Incidence and severity of serious adverse events.

    Measured: 2 years

  3. Adverse Events of Special Interest (AESI)

    Incidence and severity of adverse event of special interest.

    Measured: 2 years

  4. 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.

    Measured: 4 weeks after the CAR-T cells infusion

Secondary outcomes (12)

  1. Objective Response Rate (ORR)

    The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1.

    Measured: 2 years

  2. Disease Control Rate (DCR)

    Disease control rate (DCR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1.

    Measured: 2 years

  3. Duration of Overall Response (DOR)

    Time from documentation of disease response to disease progression.

    Measured: 2 years

  4. Progression-Free Survival (PFS)

    PFS is defined as the time from CAR-T infusion to the date of the disease progression or death from any cause.

    Measured: 2 years

  5. Overall Survival (OS)

    OS is defined as the time from CAR-T infusion to the date of death due to any cause.

    Measured: 2 years

  6. Cytokine Level in Peripheral Blood

    Level of cytokines in serum.

    Measured: 2 years

  7. Bio-distribution of Anti mesothelin CAR-T cells

    CAR copies will be measured by qPCR to evaluate the expansion and persistence of CAR-T cells in vivo.

    Measured: 2 years

  8. Tmax is time to peak CAR level in blood or bone marrow.

    Tmax is time to peak CAR level in blood or bone marrow.

    Measured: 2 years

  9. AUC0-tlast and AUC0-inf

    AUC0-tlast and AUC0-inf are area under the curve of the CAR level

    Measured: 2 years

  10. Cmax

    Cmax is the maximum CAR level in peripheral blood or bone marrow.

    Measured: 2 years

  11. Anti-drug Antibodies

    Number of participants with anti-drug antibodies.

    Measured: 2 years

  12. RP2D

    The RP2D is the optimal dose level selected for further evaluation in Phase II clinical trials, based on safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy data gathered during Phase I dose-escalation studies. It represents the dose that balances maximum therapeutic benefit with acceptable toxicity for patients.

    Measured: 4 weeks after the CAR-T cells infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2025
  2. Study start15 Oct 2024
  3. Primary completion14 Oct 2026 (estimated)
  4. Study completion14 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Accelerated titration and 3+3 design dose escalation phase followed by dose expansion phase
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07010523
Sponsor's protocol ID
[2024]TXB014
Status last verified
Feb 2025
First submitted
17 Feb 2025
Last updated
8 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A study testing Anti-mesothelin CAR-T cells, Fludarabine and Cyclophosphamide in people with Mesothelin-positive Advanced Malignant Solid Tumors, run by First Affiliated Hospital of Zhejiang University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Wenyu Wang, MD PhD (+86 0571-87237587, wywang0815@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events (AEs) (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07010523.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2025.

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