| Eligibility |
Inclusion Criteria:
1. 18 to 75 years old (including cut-off value), gender is not limited
2. 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.
3. At least one measurable lesion according to RECIST v1.1.
4. Mesothelin should be positive confirmed by Immunohistochemistry/Immunocytochemistry
(IHC/ICC) in tumor tissue samples.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy = 3 months.
7. 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%.
8. 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.
9. 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.
Exclusion Criteria:
1. 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.
2. Pregnant or lactating women.
3. 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.
4. 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.
5. 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.)
6. Patients have received anti-mesothelin CAR-T cell therapy.
7. 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.
8. 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.
9. 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.
10. 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.
11. Patients have received attenuated vaccine within 4 weeks prior to signing informed
consent.
12. Patients have received other clinical trials within 4 weeks prior to signing informed
consent.
13. 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.
14. 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.
15. For any other reasons, the patients are believed not suitable for participation in
this study by investigators.
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