Phase 1 Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors

Inclusion Criteria:

1. 18 to 70 years old,regardless of gender

2. Diagnosed Patients with malignant solid tumors confirmed histopathologically (including but not limited to mesothelioma, pancreatic cancer, biliary tract cancer,lung cancer, ovarian cancer, gastric cancer, colorectal cancer, thymus cancer,esophageal cancer, breast cancer, and endometrial cancer, etc.) who fail or cannottolerate standard treatment or lack effective treatment methods as defined by CSCOand NCCN guidelines

3. At least have one evaluable lesion;

4. Patients who Can provide tumor tissue samples or tumor samples can be obtainedthrough methods such as tumor biopsy;

5. Positive expression of MSLN in tumor cells confirmed by Immunohistochemistry (IHC)or immunocytochemistry (ICC) staining

6. Eastern Cooperative Oncology Group (ECOG) performance score at 0 or 1;

7. Life expectancy ≥ 3 months.

8. The organ function must meet the following requirements:

• Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L (Without receiving G-CSF support within 7 days prior to laboratoryexamination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 10^9/L; Hemoglobin (HGB) ≥ 80 g/L (without receiving any blood transfusion or erythropoietin stimulatingagent therapy within 7 days before the laboratory examination);Platelet count (PLT) ≥ 75 × 10^9/L (Without receiving platelet transfusion and TPO within 7days before the laboratory examination)；

• Hepatic functions: Aspartate aminotransferase (AST) and alanineaminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN)(for patients withprimary liver tumors or liver metastases ，AST and ALT≤ 5.0× ULN)；Totalbilirubin (TBIL) ≤ 1.5 × ULN(for patients with primary liver tumors or livermetastases，TBIL≤ 3.0× ULN；patients with Gilbert's Syndrome，TBIL≤3×ULN andDirect bilirubin≤ 1.5 × ULN).

• Coagulation functions: Activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

• Renal functions: Serum creatinine (Cr)≤1.5 × ULN; or Creatinine clearance rate (Ccr) ≥ 60 mL/min（Cockcroft-Gault）.

• Cardiac functions: Left ventricular ejection fraction (LVEF) > 50% (confirmedby ECHO).

• Lung fuction:Pulse oxygen saturation (SpO2) > 95% at rest without oxygenation

9. Women of childbearing potential (WCBP) must have negative results on a serumpregnancy test, and WCBP or Male who have partners of reproductive potential mustagree to use effective contraceptive methods to avoid pregnancy throughout thescreening and study period until 1 year after the last cell infusion;

10. Voluntary signing informed consent form(s) indicating that they are willing toparticipate in the study and are able to comply with the protocol.

Exclusion Criteria:

1. Have received systemic antitumor therapy involving cytotoxic chemical agents,monoclonal antibodies or immunotherapy within 4 weeks or 5 half-lives (whichever isshorter) prior to signing the informed consent form（ICF）; Have received systemicglucocorticoids (prednisone or other equivalent hormone at a dose ≥ 10 mg/day) orother treatments to suppress the immune system within 2 weeks prior to signing theICF; Have received systemic antitumor therapy involving biologics or other approvedsmall molecule targeted inhibitors within 1 week or 5 half-lives (whichever isshorter) prior to signing the ICF; Have received treatments with Chinese herbalmedicines (CHM) and Chinese proprietary medicines (CPM) that has an antitumorindication within 1 week prior to signing the ICF;

2. Pregnant or lactating women;

3. The finding of Positive hepatitis B surface antigen (HBsAg) or positive hepatitis Bcore antibody (HBcAb) and the result of quantitative HBV DNA test in peripheralblood is above the lower limit of detection (LLOD); positive Hepatitis C virus (HCV)antibody, and the result of quantitative HCV RNA test in peripheral blood is abovethe LLOD; The presence of positive Human immunodeficiency virus (HIV) antibody;positive Syphilis antibody test;

4. Patients with Epstein-Barr Virus (EBV) DNA positive.

5. Non-hematologic toxicity due to prior therapy (surgery, chemotherapy, radiation,targeted therapy, and immunotherapy, etc.) have not resolved to ≤ CTCAE grade 1 (except alopecia, peripheral sensory nerve disorders);

6. Have received any prior xenotransplantation of tissues /organs (including bonemarrow transplantation, stem cell transplantation, liver transplantation, and kidneytransplantation, etc.), except for transplants that do not require immunosuppression (e.g., corneal graft and hair transplantation, etc.);

7. Previoulsly received any anti mesothelin (MSLN) treatment and any geneticallymodified cell therapy within 6 months prior to signing the informed consent form;

8. Have undergone major surgery and not fully recovered within 4 weeks prior to signinginformed consent or have a history of severe trauma that have not recovered, orplanned to receive major surgery within 12 weeks after cell infusion;

9. Presence of known CNS metastases

10. Presence of clinically significant systemic disease (e.g., severe active infectionor significant dysfunctions of the heart, lungs, liver, nervous system, or otherorgans) that, at the discretion of the investigator, impairs the patient's abilityto tolerate the treatment specified in this trial protocol or significantlyincreases the risk of complications. Including but not limited to:

• Presence of uncontrolled severe active infection (e.g., sepsis, bacteremia, andviremia, etc.);

• Congestive heart failure classified as > class I based on New York HeartAssociation (NYHA);

• Clinically significant severe aortic stenosis and symptomatic mitral valvestenosis;

• QTc > 450 msec or QTc > 480 msec as shown by ECG in patients with bundle branchblock;

• Presence of uncontrolled clinically significant arrhythmias within 6 monthsprior to signing the ICF;

• Presence of acute coronary syndrome within 6 months prior to signing the ICF (e.g., unstable angina and myocardial infarction);

• Hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic bloodpressure ≥ 100 mmHg) or pulmonary hypertension that has not been controlled bymedication;

• Cerebrovascular accident within 6 months prior to signing informed consent,including: Transient ischemic attack (TIA), brain infarction, cerebralhemorrhage and subarachnoid hemorrhage;

• Presence of active, chronic or relapsing (within 1 year prior to signing theICF) severe autoimmune disorder or history of immune-mediated disease requiringsteroid or other immunosuppressive therapy, including but not limited tosystemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatorybowel disease, Hashimoto's thyroiditis, autoimmune thyroid disorder, andmultiple sclerosis, etc. Except: Hypothyroidism that can be controlled bythyroid hormone replacement therapy alone, skin diseases that do not requiresystemic treatment (e.g. vitiligo and psoriasis), celiac disease that isalready under control;

• Presence of any form of primary or secondary immunodeficiency, such as: Severecombined immunodeficiency (SCID);

• Possibility of bleeding due to esophageal or gastric varices as judged by theinvestigator.

11. History of severe systemic hypersensitivity reactions to the drugs/components usedin this trial [such as: fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO),low molecular dextran, and human serum albumin (HSA), etc.];

12. Have received a live attenuated vaccine within 4 weeks prior to signing the ICF;

13. Participation in another clinical trial within 4 weeks prior to signing theICF(Enrolled and given of investigational drugs/treatments);

14. History of another malignancy within the previous 5 years (except adequately treatednon-melanoma skin cancer and in situ cancer in the following sites: breast, stomach,colon, and cervical, etc.);

15. Prior neuropsychiatric disorders diagnosed by International Classification ofDiseases 11th Revision (ICD-11) criteria for mental and behavioral disorders orneuropsychiatric disorders to be excluded as assessed by the investigator, includingbut not limited to epilepsy, schizophrenia, dementia, addictive behaviors due todrugs and alcohol, etc.;

16. Presence of other conditions that, in the judgment of the investigator, wouldpreclude the patient from participating in this trial.