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Mesothelin-positive Advanced Malignant Solid TumorsPhase 1NCT05783089

MSLN-targeted CAR-T Cells in Solid Tumors.

A Phase 1 study testing Anti-mesothelin CAR-T cells in people with Mesothelin-positive Advanced Malignant Solid Tumors, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This study aims to explore the safety, tolerability and preliminary efficacy of Anti-Mesothelin CAR-T cells in subjects with Mesothelin-positive advanced malignant solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-mesothelin CAR-T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
87 participants
Where
No sites listed yet
Study dates
Apr 2023to Apr 2027
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject is≥18 years old (including cut-off value), gender is not limited
  • Solid tumors that histological diagnosis of malignancy refractory 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.
  • 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

  • Patients have received systemic therapy with cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior to signing informed consent; Patients have received systemic glucocorticoids (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive therapy within 2 weeks prior to signing informed consent; Patients have received systemic antitumor therapy with a biologic agent or other approved targeted small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to signing informed consent; Patients have received Chinese herbal medicine or Chinese patent medicine with anti-tumor indication within 1 week prior to signing informed consent.
  • 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 DNA 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.
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  • 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;
  • 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

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Hong Zhao contact

010-87787100

pumc95zhao@126.com

Zhen Huang contact

010-87787100

About this study

Official title: Anti-Mesothelin CAR-T Therapy in Subjects With Mesothelin-positive Advanced Malignant Solid Tumors.

This study aims to explore the safety, tolerability and preliminary efficacy of Anti-Mesothelin CAR-T cells in subjects with Mesothelin-positive advanced malignant solid tumors.

Read the detailed description

This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of Anti-Mesothelin CAR-T cells. Patients will be confirmed to have sufficient expression of mesothelin as part of a prescreening. The study comprises a dose-escalation component and a dose-expansion component. There are three cohorts in dose-expansion component. Cohort 1: To explore the effects of different conditioning chemotherapy regimens on safety, tolerability and efficacy; Cohort 2: To explore the effects of different administration modes (intravenous injection and local injection) on safety, tolerability and efficacy; Cohort 3: To explore the effects of combination immune checkpoint inhibitors on safety, tolerability and efficacy.

Being tested
Anti-mesothelin CAR-T cells
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

    Also called UCLM802 Cell Injection

    Anti-mesothelin CAR-T cells are autologous genetically modified T cells. Cells will be infused intravenously.

Study groups in NCT05783089
Study groupRoleWhat they receive
Anti-mesothelin CAR-T cells InjectionExperimentalAnti-mesothelin CAR-T cells Injection will be infused at a dose ranging from 0.1×10^6/Kg ～ 2.0×10^6/Kg after receiving lymphodepleting chemotherapy.
Receives: Biological: Anti-mesothelin CAR-T cells

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

    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. Identification 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 (8)

  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)

    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

  6. Bio-distribution of 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

  7. Cytokine Level in Peripheral Blood

    Level of cytokines (IP-10, IFN-γ, IL-6, IL-10, TNF-α, GM-CSF, etc.) in serum.

    Measured: 2 years

  8. Anti-drug Antibodies

    Number of participants with anti-drug antibodies.

    Measured: 2 years

Timeline

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

  1. First posted24 Mar 2023
  2. Study startApr 2023 (estimated)
  3. Primary completionApr 2025 (estimated)
  4. Study completionApr 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 1
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
87 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05783089
Sponsor's protocol ID
UCLM802-IV
Status last verified
Mar 2023
First submitted
13 Mar 2023
Last updated
24 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-mesothelin CAR-T cells in people with Mesothelin-positive Advanced Malignant Solid Tumors, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.

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 26 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: opening soon, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Hong Zhao (010-87787100, pumc95zhao@126.com), 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 NCT05783089.

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 24 Mar 2023.

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