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

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

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase 1 Study of AFP Specific T Cell Receptor Transduced T Cells Injection in Unresectable Hepatocellular Carcinoma

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Biological: AFP Specific T Cell Receptor T Cells


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to provide written informed consent. Age 18-70 years old, male or female. Patients must meet the following criteria: Histologically confirmed HCC Serum AFP >200 ng/mL Child-Pugh score ≤6 BCLC stage B and stage C or stage Ⅱa/Ⅱb and Ⅲa/Ⅲb defined by Chinese Liver Cancer Guideline（2017） Clinical confirmed relapse or progression if patient had locoregional therapy previously 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) . 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. Previous systemic therapy was discontinued at least 2 weeks before apheresis. Has at least 1 measurable lesion as defined per RECIST v1.1. HLA-A 02:01 allele positive. Liver AFP expression IHC tests: ≥20% tumor cells positive, and ≤5% non-tumor tissue positive; serum AFP ≥400ng/ml, and ≤5% non-tumor tissue positive. ECOG score ≤ 1. Expected survival > 12 weeks Left ventricular ejection fraction (LVEF) ≥ 50% (measured by echocardiography). No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air. Laboratory criteria Absolute neutrophil count (ANC) ≥ 1.5x10^9/ L Platelets≥ 60x10^9/L Hemoglobin≥ 90g/L Serum total bilirubin ≤ 2 x ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 x ULN Creatinine ≤1.5×ULN International normalized ratio (INR) or prothrombin time (PT) ≤1.5 x ULN 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. 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. Agree to abstain from alcohol during the study period No contraindications for apheresis Apheresis was received by laboratory ,and passed QC Exclusion Criteria: Have a history of allergy to cellular products. Subject has liver transplantation history. tumor volume was greater than 70% of liver tissue main portal vein carcinoma thrombus Medium to severe ascites. 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. 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 Significant clinical gastrointestinal bleeding within 4 weeks before treatment. Subjects with bone metastasis or central nervous system metastasis, or with hepatic encephalopathy, epilepsy, cerebrovascular accident and other central nervous system involvement diseases. Prior treatment with genetically modified T cell therapy or stem cell therapy. Uncontrolled active infection. Preventive antibiotics, antiviral and antifungal are permitted. Active hepatitis virus infection. HCV RNA positive. Subjects with syphilis or other acquired, congenital immunodeficiency disorders, including, but not limited to, HIV infected persons, systemic lupus erythematosus, psoriasis, etc. Heart insufficiency subjects of Grade III or IV according to NYHA classification criteria. 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. Subjects received radiotherapy within 6weeks before Leukocyte apheresis Subjects who are pregnant, lactating, or pregnant within 6 months Any other disease that may increase the risk of the subject or interfere with the results of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C-TCR055<br>Autologous C-TCR055 administered by intravenous (IV) infusion | Biological: AFP Specific T Cell Receptor T Cells<br>* Autologous T cells transduced with lentivirus encoding AFP specific TCR gene<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment related adverse events as assessed by CTCAE v4.0[Safety of C-TCR055] | Determine if treatment with C-TCR055 is safe through assessment of adverse events(AEs) and serious adverse events(SAEs) as assessed by CTCAE v4.0 | start treatment to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Overall response rate based on RECIST v1.1 | 3 months and 6 months | 
| DOR | Duration of remission | 12 months | 
| PFS | Progression free survival | 12 months | 
| OS | Overall survival | 6 months and 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Liver Cancer