HER2 Targeted HypoSti.CAR-T Cells in HER2 Positive Advanced Solid Tumors

Inclusion Criteria:

• 1. Age from 18 to 75 years with estimated life expectancy >3 months.
• 2. Histopathological confirmed advanced or metastatic solid tumors failed to at leastfirst-line treatment or initially diagnosed advanced/metastatic solid tumors that haveno NCCN guideline recommended standard first-line therapy. HER2 antigen expressionpercentage ≥ 30%.
• 3. Have at least one measurable target lesion.
• 4. Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archivalsamples within 6 months are necessary; Fresh tumor samples are preferred. Subjects arewilling to accept tumor rebiopsy in the process of this study.
• 5. Previous treatment must be completed for more than 4 weeks prior to the enrollmentof this study, and subjects have recovered to <= grade 1 toxicity.
• 6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 atthe time of enrollment.
• 7. Have adequate organ function, which should be confirmed within 2 weeks prior to thefirst dose of study drugs.
• 8. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.
• 9. Ability to understand and sign a written informed consent document.
• 10. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and upto 90 days after the last dose of the drug.

Exclusion Criteria:

• 1. Active, known or suspected autoimmune diseases.
• 2. Known brain metastases or active central nervous system (CNS). Subjects with CNSmetastases who were treated with radiotherapy for at least 3 months prior toenrollment, have no central nervous symptoms and are off corticosteroids, are eligiblefor enrollment, but require a brain MRI screening.
• 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisoneequivalent) or other immunosuppressive medications within 14 days of enrollment.
• 4. History of severe hypersensitive reactions to other monoclonal antibodies.
• 5. History of allergy or intolerance to study drug components.
• 6. Substance abuse, medical, psychological or social conditions that may interferewith the patient's participation in the study or evaluation of the study results.
• 7. History or concurrent condition of interstitial lung disease of any grade orseverely impaired pulmonary function.
• 8. Uncontrolled intercurrent illness, including ongoing or active systemic infection,symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatricillness/social situations and any other illness that would limit compliance with studyrequirements and jeopardize the safety of the patient.
• 9. History of human immunodeficiency virus (HIV) infection or acquiredimmunodeficiency syndrome (AIDS).
• 10. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancytest performed within 7 days before the enrollment, and a negative result must bedocumented.
• 11. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT forcuratively treated cervical cancer in situ, non-melanoma skin cancer, superficialbladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invadeslamina propria)].
• 12. Vaccination within 30 days of study enrollment.
• 13. Active bleeding or known hemorrhagic tendency.
• 14. Subjects with unhealed surgical wounds for more than 30 days.
• 15. Being participating any other trials or withdraw within 4 weeks.