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Redirected HBV-Specific T Cells in Patients With HBV-related HCC (SAFE-T-HBV) (SAFE-T-HBV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04745403
Recruitment Status : Not yet recruiting
First Posted : February 9, 2021
Last Update Posted : February 9, 2021
Sponsor:
Information provided by (Responsible Party):
Lion TCR Pte. Ltd.

Study Description
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Brief Summary:
This is a single center. single arm, open-label study to determine the safety of mRNA modified HBV-TCR redirected T-cells and to analyze the changes in tumor microenvironment caused by these HBV-TCR redirected T-cells in subjects with HBV-related HCC who are not amenable to/failed conventional treatment.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: mRNA HBV/TCR T-cells Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Safety and Tolerability Study of Redirected HBV-Specific T Cells in Patients With Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (SAFE-T-HBV)
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : July 1, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: mRNA HBV/TCR T-cells
Escalating regime from 1x10e5 to 5-10x10e6 cells/kg bodyweight (BW) every 2 weeks.
 Drug: mRNA HBV/TCR T-cells

Study Infusion

The first dose of mRNA HBV-TCR T-cells at dose 1x10e5/kg BW will be infused on Day 0, and subsequently incremental doses on Day 14 and 28, up to the dose of 5-10x10e6/kg BW.


Outcome Measures
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Primary Outcome Measures :
  1. Safety evaluation of TCR-T treatment [ Time Frame: Start of treatment until 28 days post last dose ]
    Based on assessments of adverse events (AEs) and serious AEs


Secondary Outcome Measures :
  1. Analysis of modifications of tumour microenvironment caused by TCR-T treatment using biopsy samples [ Time Frame: Start of treatment until 14 days post last dose ]
    Based on immune gene expression changes determined by RNA sequencing

  2. Analysis of modifications of tumour microenvironment caused by TCR-T treatment using blood samples [ Time Frame: Start of treatment until 14 days post last dose ]
    Based on changes in level of serum cytokines


Eligibility Criteria
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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  2. Presence of primary hepatocellular carcinoma in the liver with presence of measurable tumour by RECIST 1.1 criteria, that is not amenable to, or failed, conventional treatment options
  3. Detectable HBV DNA integrations in the HCC tumour biopsy
  4. Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points)
  5. HLA class 1 profile matching HLA-class I restriction element of the available T cell receptors (restricted by HLA-A0201, HLA-B5801, HLA-Cw0801)
  6. Life expectancy of at least 3 months
  7. Serum anti HBV core antibody positive (at any historical time)
  8. Adequate organ function as defined below: a. Differential white blood counts within normal reference ranges b. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 150 IU/ml c. Total conjugated serum bilirubin ≤ upper limit normal (ULN) d. eGFR ≥ 60ml/minute e. Hemoglobin > 10.0 mg/ dl f. Platelet count ≥ 100,000/ μl
  9. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
  10. Willing to undergo biopsy of non-tumour and tumour liver tissue before and after treatment
  11. Sexually active subjects must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 28 days after the last dose of study drug
  12. Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy
  13. Willing and able to comply with all study procedures

Exclusion Criteria:

  1. Brain metastasis
  2. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
  3. Use of checkpoint inhibitors within 6 months of baseline liver biopsy procedure
  4. Alterations of concomitant medications within 3 months of baseline liver biopsy procedure.
  5. Likelihood to require any immunosuppressive treatments during the period of the clinical trial.
  6. Patient's last RFA/TACE, or Y90 therapy is less than 3 and 6 months ago, respectively.
  7. Decompensated cirrhosis Child-Pugh B or C (7 - 15 points)
  8. Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
  9. Use of any investigational product (IP) or investigational medical device within 30 days of study drug administration
  10. Poorly controlled medical illness that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
  11. Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic pressure >110 mmHg, despite optimal medical management
  12. Serum HBV DNA levels ≥ 200 IU/ml at screening
  13. Serum HBsAg levels ≥ 10,000 IU/ml at screening
  14. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
  15. Substance abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the study or evaluation of study results.
  16. Any condition or active infections which, in the investigator's opinion, makes the subject unsuitable for trial participation
  17. Women who are pregnant or breast-feeding
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04745403


Contacts
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Contact: Royce Fam 69260818 royce.fam@liontcr.com

Locations
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Singapore
Singapore General Hospital
Singapore, Singapore, 169608
Contact: Thinesh L Krishnamoorthy    62223322    thinesh.l.krishnamoorthy@singhealth.com.sg   
Contact       thinesh.l.krishnamoorthy@singhealth.com.sg   
Principal Investigator: Thinesh L Krishnamoorthy         
Sponsors and Collaborators
Lion TCR Pte. Ltd.
More Information
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Publications of Results:

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Responsible Party: Lion TCR Pte. Ltd.
ClinicalTrials.gov Identifier: NCT04745403    
Other Study ID Numbers: LTCR-HCC-3-3
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: February 9, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lion TCR Pte. Ltd.:
Hepatitis B virus
Hepatocellular Carcinoma
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
 Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases