Clinical Trials /

AFPᶜ³³²T in Advanced HCC

NCT03132792

Description:

This first time in human study is intended for men and women between 18 and 75 years of age who have advanced liver cancer which has grown or returned after being treated or another AFP expressing tumor. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer or other AFP expressing tumor types. This study is for subjects who have a blood test positive for appropriate HLA-A*02 P Group and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein (Liver only). The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AFPᶜ³³²T in Advanced HCC
  • Official Title: A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFPᶜ³³²T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC)

Clinical Trial IDs

  • ORG STUDY ID: ADP-0033-001
  • NCT ID: NCT03132792

Conditions

  • Hepatocellular Cancer

Purpose

This first time in human study is intended for men and women at least 18 years of age who have advanced liver cancer which has grown or returned after being treated. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer. This study is for subjects who have a blood test positive for appropriate HLA-A*02 and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.

Trial Arms

NameTypeDescriptionInterventions
Autologous genetically modified AFPᶜ³³²T cellsExperimental

    Eligibility Criteria

            Key Inclusion Criteria:
    
              1. Histologically confirmed HCC, not amenable to transplant, resection. Subjects may
                 undergo loco-regional therapy after enrollment but not at time of lymphodepletion.
    
              2. Measurable disease according to RECIST 1.1 criteria prior to lymphodepletion.
    
              3. Progressive disease following or intolerant of or refuses standard of care systemic
                 therapy prior to lymphodepletion.
    
              4. Positive for HLA-A*02:01or HLA-A*02:642 allele.
    
              5. Subjects will be eligible for enrollment if they meet either one of these AFP
                 expression criteria:
    
                   -  AFP expression of ≥1+ in ≥20% of tumor cells by immunohistochemistry and their
                      non-cancerous liver tissue has ≤5% cells stained for AFP at any intensity by
                      immunohistochemistry.
    
                   -  Serum AFP levels of ≥400ng/mL and their non-cancerous liver tissue has ≤5% cells
                      stained for AFP at any intensity by immunohistochemistry.
    
              6. Life expectancy of > 4 months
    
              7. Child-Pugh score ≤ 6
    
              8. Eastern Cooperative Oncology Group (ECOG) 0-1
    
              9. Subject must have adequate organ function as defined in the protocol.
    
            Key Exclusion Criteria:
    
              1. Positive for any of the HLA-A*02 allele other than HLA-A*02:01 or HLA-A*02:642 (except
                 null alleles or HLA-A*02:03) or the following alleles: HLA-C*04:04 or HLA-B*51:03.
    
              2. Prior liver transplant
    
              3. Clinically or radiographically detectable ascites (beyond trace/rim of ascites) or
                 ascites requiring medication
    
              4. Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring
                 medication
    
              5. Subject has brain metastases.
    
              6. Other active malignancy besides HCC within 3 years.
          
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Number of subjects with dose-limiting toxicity (DLT) and adverse events (AEs) and determination of optimally tolerated dose range, including serious adverse events (SAE).
    Time Frame:2 years
    Safety Issue:
    Description:Determine if treatment with autologous genetically modified T cells, (AFPᶜ³³²T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments including chemistry, hematology, coagulation, cardiac assessments including ECG, and cardiac Troponin

    Secondary Outcome Measures

    Measure:Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR)
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
    Measure:Interval between the date of first T cell infusion dose and first documented evidence of CR or PR
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of time to first response
    Measure:Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of response
    Measure:Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of duration of stable disease
    Measure:Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of progression-free survival
    Measure:Interval between the date of first T cell infusion and date of disease progression or death due to any cause
    Time Frame:2 years
    Safety Issue:
    Description:Evaluation of the efficacy of the treatment by assessment of overall survival

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Adaptimmune

    Trial Keywords

    • Alpha-fetoprotein
    • Cell Therapy
    • T Cell Therapy
    • SPEAR T Cell
    • Immuno-oncology
    • Metastatic
    • Previously treated
    • T Cell Receptor

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