Anti-HER2 CAR-T Cell Injection in Patients With HER2-positive Advanced Malignant Solid Tumors

Inclusion Criteria:

• 1. 18 to 70 years old (including cut-off value), gender is not limited.

2. Solid tumors that histological diagnosis of malignancy refractory to, orrelapsing after standard therapy, including but not limited to gastric cancer,biliary system tumors, bladder cancer, ovarian cancer, endometrial cancer, cervicalcancer, colorectal cancer, breast cancer, lung cancer, esophageal cancer, etc.

3. At least one measurable lesion according to RECIST v1.1.

4. HER2 should be positive confirmed by Immunohistochemistry in tumor tissuesamples.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Life expectancy ≥ 3 months.

7. The organ function must meet the protocol requirements.

8. Female participants of childbearing potential must undergo a pregnancy test andthe results must be negative. Female participants of childbearing potential or maleparticipants whose sex partner has childbearing potential must be willing to useeffective methods of contraception from screening period to at least 1 year afterinfusion.

9. Participants must be able to understand the protocol and be willing to enroll thestudy, sign the informed consent, and be able to comply with the study and follow-upprocedures.

Exclusion Criteria:

• 1. Pregnant or lactating women.

2. Patients with hepatitis B surface antigen (HBsAg) positive. Patients who ishepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA inperipheral blood is higher than the lower limit of detection. Patients who ishepatitis C virus (HCV) antibody positive and quantification of HCV DNA inperipheral blood is higher than the lower limit of detection. Patients with humanimmunodeficiency virus (HIV) antibody positive, or syphilis antibody positive.

3. The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy,targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according toCTCAE, except for hair loss and peripheral sensory nerve disorders.

4. Have received any allogeneic tissue/organ transplantation (including bone marrowtransplantation, stem cell transplantation, liver transplantation, kidneytransplantation), except for the transplantation that does not requireimmunosuppressive therapy (such as: corneal transplantation, hair transplantation.)

5. Patients have received anti-HER2 CAR-T cell therapy.

6. Patients who have history of major surgery and unrecovered severe trauma within 4weeks prior to signing informed consent; or plan to have major surgery within 12weeks of cell therapy.

7. Presence of known central nervous system metastases, but the following patientswill be allowed: a) Asymptomatic brain metastases; b) Clinically stable (noradiographic progression within 4 weeks before apheresis and return of anyneurologic symptoms to baseline), and with no need for corticosteroids or othertreatment for brain metastases for ≥ 4 weeks.

8. Patients with clinically significant systemic disease (such as: severe activeinfection or significant cardiac, pulmonary, hepatic, nervous system, or other organdysfunction) that evaluated by the investigator would impair the patients' abilityto tolerate the treatments used in this study or significantly increase the risk ofcomplications.

9. 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.

10. Patients have received attenuated vaccine within 4 weeks prior to signinginformed consent.

11. Patients have received other clinical trials within 4 weeks prior to signinginformed consent.

12. History of another malignancy tumor within the previous five years, except foradequately treated non-melanoma skin cancer, carcinoma in situ of bladder, stomach,colon, cervix/dysplasia, melanoma, or breast.

13. History of neuropsychiatric diseases diagnosed by the ICD-11 criteria orevaluated by investigator, including but not limited to epilepsy, schizophrenia,dementia, drug and alcohol addictions.

14. For any other reasons, the patients are believed not suitable for participationin this study by investigators.