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出境医 / 临床实验 / AFP Specific T Cell Receptor Transduced T Cells Injection(C-TCR055) in Unresectable Hepatocellular Carcinoma

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

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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: AFP Specific T Cell Receptor T Cells Phase 1

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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of AFP Specific T Cell Receptor Transduced T Cells Injection in Unresectable Hepatocellular Carcinoma
Actual Study Start Date : August 6, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : April 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: C-TCR055
Autologous C-TCR055 administered by intravenous (IV) infusion
 Biological: AFP Specific T Cell Receptor T Cells
Autologous T cells transduced with lentivirus encoding AFP specific TCR gene
Outcome Measures
Primary Outcome Measures :
  1. Incidence of treatment related adverse events as assessed by CTCAE v4.0[Safety of C-TCR055] [ Time Frame: start treatment to 12 months ]
    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


Secondary Outcome Measures :
  1. ORR [ Time Frame: 3 months and 6 months ]
    Overall response rate based on RECIST v1.1

  2. DOR [ Time Frame: 12 months ]
    Duration of remission

  3. PFS [ Time Frame: 12 months ]
    Progression free survival

  4. OS [ Time Frame: 6 months and 12 months ]
    Overall survival


Other Outcome Measures:
  1. DCR [ Time Frame: 3 months and 6 months ]
    Disease Control Rate based on RECIST v1.1


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Yuhong Zhou, MD, Ph.D 86-021-64041990 zhou.yuhong@zs-hospital.sh.cn

Locations
Layout table for location information
China, Shanghai
Fudan University Affiliated ZhongShan Hospital Recruiting
Shanghai, Shanghai, China, 200032
Contact: Yuhong Zhou, Ph.D       zhou.yuhong@zs-hospital.sh.cn   
Sponsors and Collaborators
Cellular Biomedicine Group Ltd.
Shanghai Zhongshan Hospital
Tracking Information
First Submitted Date  ICMJE May 28, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date April 7, 2020
Actual Study Start Date  ICMJE August 6, 2019
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019) 		Incidence of treatment related adverse events as assessed by CTCAE v4.0[Safety of C-TCR055] [ Time Frame: start treatment to 12 months ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2019)
  • ORR [ Time Frame: 3 months and 6 months ]
    Overall response rate based on RECIST v1.1
  • DOR [ Time Frame: 12 months ]
    Duration of remission
  • PFS [ Time Frame: 12 months ]
    Progression free survival
  • OS [ Time Frame: 6 months and 12 months ]
    Overall survival
Original Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • ORR and DCR [ Time Frame: 3 months and 6 months ]
    Overall response rate and Disease Control Rate based on RECIST v1.1
  • DOR [ Time Frame: 12 months ]
    Duration of remission
  • PFS [ Time Frame: 12 months ]
    Progression free survival
  • OS [ Time Frame: 6 months and 12 months ]
    Overall survival
Current Other Pre-specified Outcome Measures
 (submitted: June 2, 2019) 		DCR [ Time Frame: 3 months and 6 months ]
Disease Control Rate based on RECIST v1.1
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AFP Specific T Cell Receptor Transduced T Cells Injection(C-TCR055) in Unresectable Hepatocellular Carcinoma
Official Title  ICMJE A Phase 1 Study of AFP Specific T Cell Receptor Transduced T Cells Injection in Unresectable Hepatocellular Carcinoma
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatocellular Carcinoma
Intervention  ICMJE Biological: AFP Specific T Cell Receptor T Cells
Autologous T cells transduced with lentivirus encoding AFP specific TCR gene
Study Arms  ICMJE Experimental: C-TCR055
Autologous C-TCR055 administered by intravenous (IV) infusion
Intervention: Biological: AFP Specific T Cell Receptor T Cells
Publications * Luo X, Cui H, Cai L, Zhu W, Yang WC, Patrick M, Zhu S, Huang J, Yao X, Yao Y, He Y, Ji Y. Selection of a Clinical Lead TCR Targeting Alpha-Fetoprotein-Positive Liver Cancer Based on a Balance of Risk and Benefit. Front Immunol. 2020 Apr 27;11:623. doi: 10.3389/fimmu.2020.00623. eCollection 2020.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2019) 		9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yuhong Zhou, MD, Ph.D 86-021-64041990 zhou.yuhong@zs-hospital.sh.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03971747
Other Study ID Numbers  ICMJE 0421-011
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cellular Biomedicine Group Ltd.
Study Sponsor  ICMJE Cellular Biomedicine Group Ltd.
Collaborators  ICMJE Shanghai Zhongshan Hospital
Investigators  ICMJE Not Provided
PRS Account Cellular Biomedicine Group Ltd.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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