AFP Specific T Cell Receptor Transduced T Cells Injection(C-TCR055) in Unresectable Hepatocellular Carcinoma

A phase 1 study that aimed to assess the safety and anti-tumor activity of C-TCR055 injection in unresectable HCC patients.

This study plans to enroll 9 patients to assess the safety of C-TCR055. Subjects who meet the eligibility criteria will receive a single dose of C-TCR055 injection, and will be followed up post treatment for safety monitoring. The follow up period will last 12 months.

Eligibility Criteria:
Inclusion Criteria:

1. Able to provide written informed consent.
2. Age 18-70 years old, male or female.
3. Patients must meet the following criteria:

   1. Histologically confirmed HCC
   2. Serum AFP \>200 ng/mL
   3. Child-Pugh score ≤6
   4. BCLC stage B and stage C or stage Ⅱa/Ⅱb and Ⅲa/Ⅲb defined by Chinese Liver Cancer Guideline（2017）
   5. Clinical confirmed relapse or progression if patient had locoregional therapy previously
   6. Systemic therapy failed HCC Subject: those who received standardized systemic treatment for unresectable HCC and subsequently relapsed/progressed, or were intolerable or unwilling to receive treatment. Front-line system treatment should be approved in China (sorafenib, lenvastinib, platinum-containing chemotherapy regimen, regofinil)
   7. . Local treatment (including surgery, ablation, interventional therapy, local radiotherapy, etc.) must be completed at least 4 weeks before apheresis, and there is no unhealed wound.
   8. Previous systemic therapy was discontinued at least 2 weeks before apheresis.
4. Has at least 1 measurable lesion as defined per RECIST v1.1.
5. HLA-A 02:01 allele positive.
6. Liver AFP expression IHC tests:

   1. ≥20% tumor cells positive, and ≤5% non-tumor tissue positive;
   2. serum AFP ≥400ng/ml, and ≤5% non-tumor tissue positive.
7. ECOG score ≤ 1.
8. Expected survival \> 12 weeks
9. Left ventricular ejection fraction (LVEF) ≥ 50% (measured by echocardiography).
10. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
11. Laboratory criteria

    1. Absolute neutrophil count (ANC) ≥ 1.5x10\^9/ L
    2. Platelets≥ 60x10\^9/L
    3. Hemoglobin≥ 90g/L
    4. Serum total bilirubin ≤ 2 x ULN
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 x ULN
    6. Creatinine ≤1.5×ULN
    7. International normalized ratio (INR) or prothrombin time (PT) ≤1.5 x ULN
12. If patient has previous HBV infection, patient should receive antivirals treatment following treatment guidelines during study period, and the HBV DNA copies should below the detection limit at screening.
13. Female subjects in childbearing age, their serum or urine pregnancy test must be negative, all subjects must agree to take effective contraceptive measures during the trial.
14. Agree to abstain from alcohol during the study period
15. No contraindications for apheresis
16. Apheresis was received by laboratory ,and passed QC

Exclusion Criteria:

1. Have a history of allergy to cellular products.
2. Subject has liver transplantation history.
3. tumor volume was greater than 70% of liver tissue
4. main portal vein carcinoma thrombus
5. Medium to severe ascites.
6. subjects received other anti-tumor systemic therapy except standard systemic therapy. Or subjects received immunocheckpoint inhibitors was less than 6 weeks or 2 drug half-lives.
7. Subject has other primary cancer except for the following:

   A. Non-melanoma cured by excision, such as basal cell skin cancer. B. Cured in situ cancers such as cervical cancer, bladder cancer or breast cancer
8. Significant clinical gastrointestinal bleeding within 4 weeks before treatment.
9. Subjects with bone metastasis or central nervous system metastasis, or with hepatic encephalopathy, epilepsy, cerebrovascular accident and other central nervous system involvement diseases.
10. Prior treatment with genetically modified T cell therapy or stem cell therapy.
11. Uncontrolled active infection. Preventive antibiotics, antiviral and antifungal are permitted.
12. Active hepatitis virus infection. HCV RNA positive.
13. Subjects with syphilis or other acquired, congenital immunodeficiency disorders, including, but not limited to, HIV infected persons, systemic lupus erythematosus, psoriasis, etc.
14. Heart insufficiency subjects of Grade III or IV according to NYHA classification criteria.
15. Subjects received systemic therapeutic steroid doses (except for the recent or current use of inhaled steroids) or other immunotherapy (such as interleukin-interferon, thymosin, etc.) within 2 weeks before Leukocyte apheresis.
16. Subjects received radiotherapy within 6weeks before Leukocyte apheresis
17. Subjects who are pregnant, lactating, or pregnant within 6 months
18. Any other disease that may increase the risk of the subject or interfere with the results of the study.