A Phase I Trial of CCT303-406 in Patients With Relapsed or Refractory HER2 Positive Solid Tumors

Inclusion Criteria:

1. Patients with willingness to be in the study and follow all study procedures, andcapable of providing informed consent

2. Male or female aged 18-70 years

3. Patients with stage IV (according to the 8th edition of AJCC) advanced solid tumormalignancies that have failed standard treatment of relapsed or difficult-to-treatsolid tumors confirmed by histology or cytology

4. At least one measurable lesion, i.e. the length of non-lymph node lesions examinedaccording to CT cross-sectional scanning or magnetic resonance imaging (MRI), or theshort diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1

5. Tumors with HER2 IHC 3+ in≥50% of all tumor cells as determined by IHC according tothe Breast Cancer HER2 Testing (2019 edition) and the Gastric Cancer HER2 Testing (2016 edition); For HER2 IHC 3+ tumors other than gastric and breast cancers, FISHis required to confirm HER2 expression; For relapsed patients after HER2-targetedtherapies, biopsy and IHC are required to confirm HER2 expression per enrollmentcriteria.

6. ECOG Performance Status 0-1

7. Expected survival greater than 12 weeks

8. Adequate organ and hematopoietic system functions to meet the followingrequirements:

• Hemoglobin (HGB) s 90 g/L, no blood transfusions within two weeks;

• White blood cell (WBC) count≥2.5×109/L

• Absolute Neutrophil Count (ANC) ≥1.5 x 109/L

• Platelet (PLT) count ≥80-109/L

• Total bilirubin (TBIL) ≤3.0ng/dL or ≤5 ULN

• ALT and AST ≤5 ULN; for liver metastasis, ALT and AST ≤5 ULN

• Creatinine (Cr) ≤1.5 x ULN; or creatinine removal rate (CrCl) ≥50 mL/min

9. LVEF≥50%

10. Serum troponin T <0.03 ng/mL

11. PT: INR < 1.7 or extended PT to normal value < 4s

12. Normal language, recognition and consciousness assessed by investigator duringscreening phase

13. Capable of receiving treatment and follow-up, including treatment in the clinicalcenter;

14. Female subjects of childbearing age must take acceptable measures to minimize thelikelihood of pregnancy during the trial. The results of serum or urine pregnancytest must be negative

15. Female subjects must not be in the lactation period.

Exclusion Criteria:

1. Females with pregnancy or in lactation period

2. Patients with active hepatitis B, or active hepatitis C

3. HIV positive

4. Other active infections of clinical significance

5. Patients receiving in situ surgery within 3 months

6. Patients with the following previous or accompanying diseases:

• Patients diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases withimmune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoidarthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis

7. Patients with ≥Grade 2 peripheral neuronal diseases (according to NCI-CTCAE v5.0)

8. Patients with any mental illness, including dementia, mental changes, which maycause difficulties understanding the informed consent and related questionnaires

9. Patients with serious uncontrollable diseases, which may interfere with thetherapies in this study

10. Patients with other active malignancies in the past 5 years excluding those withcompletely cured basal or squamous skin cancers, superficial bladder cancers orprimary breast cancers without need of follow-up treatment

11. Patients receiving systemic steroids or steroid inhalants

12. Patients who have received tumor immunotherapy (including monoclonal antibody orcell therapy) in the past 4 weeks

13. Patients allergic to immunotherapies or related drugs

14. Patients with metastatic lesions in meninges or central nervous system, or clearevidence of central nervous system diseases with continous significant symptoms inthe last 6 months

15. Patients with NYHA class II heart failure, or hypertension incontrollable bystandard care, or medical history of myocarditis, or heart attack within a year

16. Patients who have received or are going to receive organ transplantation

17. Patients with active bleeding

18. Patients with incontrollable pleural or abdominal fluid that needs clinicaltreatment or intervention

19. Patients having undergone major surgery within 4 weeks or have not fully recoveredfrom prior surgery

20. Patients that have received radiotherapy within 4 weeks, excluding those whoreceived local irradiation for the peripheral bone metastatic lesions for more than 2 weeks, and recovered from all acute toxicities of radiotherapy

21. Patients that have received anthracyclines within 8 weeks

22. Patients as determined by the investigators to be inappropriate for the study