CCT301-38 CAR-T in Patients With Relapsed or Refractory AXL Positive Sarcomas

Prior treatment

• Subjects with the following previous or accompanying diseases:
  • Subjects 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 (e.g. Wegena granuloma);
• Patients with previous diagnosis as motor neuron disease caused by autoimmunity;
• Patients previously suffered from toxic epidermal necrolysis (TEN)
• Subjects receiving systemic steroids or steroid inhalants;
• Patients who have received tumor immunotherapy (including monoclonal antibody against PD-1, PD-L1, PD-L2, CD137 or CTLA-4, or cell therapy) in the past 4 weeks;
• Subjects who have received or are going to receive organ transplantation;

Other illness

• Subjects with active hepatitis B, or active hepatitis C. Subjects with undetectable HBV DNA or HCV RNA after anti-virus treatment can be enrolled;
• HIV positive;
• Other active infections of clinical significance;
• 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;
• Subjects 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 continuous 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 with active bleeding;

Other

• Females with pregnancy or in lactation period;
• Patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention;
• Patients as determined by the investigators to be inappropriate for the study.

• 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 unresectable, locally advanced or metastatic relapse/refractory sarcomas that have failed at least the front line standard treatment 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, and the FDG PET signal from the measurable lesion is > 3 SUV;
• Tumors with AXL positive (IHC 1+ or greater) in ≥50% of all tumor cells. A new biopsy is required if the sample is over one year.
• 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) ≥1.5×109/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;
• 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;