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

A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT301-38) in Patients With Relapsed or Refractory AXL Positive Sarcomas

This clinical study is to investigate the safety and tolerability of CCT301-38 CAR modified autologous T cells (CCT301-38) in subjects with relapsed or refractory AXL positive sarcomas

This study is an open label, single-center Phase I dose escalation trial to assess the safety, tolerability, DLT and MTD of CCT301-38 cell therapy in patients with AXL positive relapsed or refractory sarcomas.

Subjects that meet inclusion criteria with positive AXL biopsy (IHC 1+ or greater in ≥50% tumor cells) will receive CCT301-38 according to the 3+3 dose escalation design.

Inclusion Criteria:

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

2. Male or female aged 18-70 years;

3. 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;

4. 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;

5. 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.

6. ECOG Performance Status 0-1;

7. Expected survival greater than 12 weeks;

8. 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;

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

10. Normal language, recognition and consciousness assessed by investigator during screening phase;

11. Capable of receiving treatment and follow-up, including treatment in the clinical center;

Exclusion Criteria:

1. Females with pregnancy or in lactation period;

2. Subjects with active hepatitis B, or active hepatitis C. Subjects with undetectable HBV DNA or HCV RNA after anti-virus treatment can be enrolled;

3. HIV positive;

4. Other active infections of clinical significance;

5. 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);

6. Patients with previous diagnosis as motor neuron disease caused by autoimmunity;

7. Patients previously suffered from toxic epidermal necrolysis (TEN)

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

9. Patients with serious uncontrollable diseases, which may interfere with the therapies in this study;

10. 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;

11. Subjects receiving systemic steroids or steroid inhalants;

12. 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;

13. Subjects allergic to immunotherapies or related drugs;

14. 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;

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

16. Subjects 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 clinical treatment or intervention;

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