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

This is a single arm, open label, dose escalation clinical study to evaluate the safety and preliminary therapeutic efficacy of CCT303-406 cells in adult subjects with HER2 positive relapsed or refractory stage IV metastatic solid tumors.

Subjects that meet inclusion criteria with positive biopsy HER2 (IHC 3+ in ≥50% tumor cells) will receive CCT303-406 according to the 3+3 dose escalation design.

Inclusion criteria

• Patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent
• Male or female aged 18-70 years
• Patients with stage IV (according to the 8th edition of AJCC) advanced solid tumor malignancies that have failed standard treatment of relapsed or difficult-to-treat solid tumors confirmed by histology or cytology
• At least one measurable lesion, i.e. the length of non-lymph node lesions examined according to CT cross-sectional scanning or magnetic resonance imaging (MRI), or the short diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1
• Tumors with HER2 IHC 3+ in≥50% of all tumor cells as determined by IHC according to the 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, FISH is required to confirm HER2 expression; For relapsed patients after HER2-targeted therapies, biopsy and IHC are required to confirm HER2 expression per enrollment criteria.
• ECOG Performance Status 0-1
• Expected survival greater than 12 weeks
• Adequate organ and hematopoietic system functions to meet the following requirements:

• 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
• LVEF≥50%
• Serum troponin T <0.03 ng/mL
• PT: INR < 1.7 or extended PT to normal value < 4s
• Normal language, recognition and consciousness assessed by investigator during screening phase
• Capable of receiving treatment and follow-up, including treatment in the clinical center;
• Female subjects of childbearing age must take acceptable measures to minimize the likelihood of pregnancy during the trial. The results of serum or urine pregnancy test must be negative
• Female subjects must not be in the lactation period.

Exclusion criteria

• Females with pregnancy or in lactation period
• Patients with active hepatitis B, or active hepatitis C
• HIV positive
• Other active infections of clinical significance
• Patients receiving in situ surgery within 3 months
• 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 with immune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis
• Patients with ≥Grade 2 peripheral neuronal diseases (according to NCI-CTCAE v5.0)
• Patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires
• Patients with serious uncontrollable diseases, which may interfere with the therapies in this study
• Patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment
• Patients receiving systemic steroids or steroid inhalants
• Patients who have received tumor immunotherapy (including monoclonal antibody or cell therapy) in the past 4 weeks
• Patients allergic to immunotherapies or related drugs
• Patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continous significant symptoms in the last 6 months
• Patients with NYHA class II heart failure, or hypertension incontrollable by standard care, or medical history of myocarditis, or heart attack within a year
• Patients who have received or are going to receive organ transplantation
• Patients with active bleeding
• Patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention
• Patients having undergone major surgery within 4 weeks or have not fully recovered from prior surgery
• Patients that have received radiotherapy within 4 weeks, excluding those who received local irradiation for the peripheral bone metastatic lesions for more than 2 weeks, and recovered from all acute toxicities of radiotherapy
• Patients that have received anthracyclines within 8 weeks
• Patients as determined by the investigators to be inappropriate for the study