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TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

Primary Purpose

Recurrent Hepatocellular Carcinoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

TCR-T cells

About this trial

This is an interventional treatment trial for Recurrent Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis as hepatocellular carcinoma (HCC).
Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation.
Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA.
HLA profile matching with HLA-class I restriction element of the available T cell receptors.
ECOG performance status ≤ 2.
Laboratory criteria:
1. Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN.
2. Neutrophil cell number ≥1.5×10^9/L.
3. Platelet count ≥100×10^9/L.
Ability to provide informed consent.
Willing and able to comply with all study procedures.

Exclusion Criteria:

Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
Likelihood to require steroid treatment during the period of the clinical trial.
Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples.
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR- T, stem cells or combined therapy of the kind within 28 days prior to start of treatment.
Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study.

Sites / Locations

The First Affiliated Hospital of Sun-Yat Sen University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HBV/ TCR T cell infusion

Arm Description

Autologous T cells with HBV antigen-specific TCR

Outcomes

Primary Outcome Measures

Safety evaluation of the TCR-T treatment

Incidence of adverse events/serious adverse events

Secondary Outcome Measures

Overall Response Rate

Tumour assessment will be according to RECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to RECIST v1.1 from baseline.

Progression-free survival (PFS)

1-year PFS is measured by the number of patients with stable disease after 1 year, using RECIST v1.1.

Overall survival (OS)

OS is defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for two years.

Full Information

NCT ID

NCT04677088

First Posted

December 16, 2020

Last Updated

December 16, 2020

Sponsor

Xiaoshun He

Collaborators

Lion TCR Pte. Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04677088

Brief Title

TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

Official Title

Phase I Study of T Cell Receptor-Redirected T Cells With Recurrent HBV Treatment in Patients-Related Hepatocellular Carcinoma in Post Liver Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Unknown status

Study Start Date

March 29, 2018 (Actual)

Primary Completion Date

February 18, 2020 (Actual)

Study Completion Date

December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Xiaoshun He

Collaborators

Lion TCR Pte. Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a single-arm and open-label study to assess the safety, tolerability and primary efficacy of the HBV specific T cell receptor (HBV/TCR) redirected T cell in patients with recurrent Hepatitis B virus (HBV) related hepatocellular carcinoma post liver transplantation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Recurrent Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HBV/ TCR T cell infusion

Arm Type

Experimental

Arm Description

Autologous T cells with HBV antigen-specific TCR

Intervention Type

Biological

Intervention Name(s)

TCR-T cells

Intervention Description

Patients will receive 1 x 10^4 cells/kg to 5 x 10^6 cells/kg bodyweight of TCR redirected T cells by IV infusion.

Primary Outcome Measure Information:

Title

Safety evaluation of the TCR-T treatment

Description

Incidence of adverse events/serious adverse events

Time Frame

Start of Treatment until 28 days post last dose

Secondary Outcome Measure Information:

Title

Overall Response Rate

Description

Tumour assessment will be according to RECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to RECIST v1.1 from baseline.

Time Frame

Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment.

Title

Progression-free survival (PFS)

Description

1-year PFS is measured by the number of patients with stable disease after 1 year, using RECIST v1.1.

Time Frame

Start of treatment until disease progression, and at 6-month and 1-year.

Title

Overall survival (OS)

Description

OS is defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for two years.

Time Frame

Start of treatment until disease progression, and at 6-month and 1-year.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis as hepatocellular carcinoma (HCC). Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation. Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA. HLA profile matching with HLA-class I restriction element of the available T cell receptors. ECOG performance status ≤ 2. Laboratory criteria: Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN. Neutrophil cell number ≥1.5×10^9/L. Platelet count ≥100×10^9/L. Ability to provide informed consent. Willing and able to comply with all study procedures. Exclusion Criteria: Second primary malignancy that is clinically detectable at the time of consideration for study enrolment. Likelihood to require steroid treatment during the period of the clinical trial. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection. Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR- T, stem cells or combined therapy of the kind within 28 days prior to start of treatment. Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study.

Facility Information:

Facility Name

The First Affiliated Hospital of Sun-Yat Sen University

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

30711630

Citation

Tan AT, Yang N, Lee Krishnamoorthy T, Oei V, Chua A, Zhao X, Tan HS, Chia A, Le Bert N, Low D, Tan HK, Kumar R, Irani FG, Ho ZZ, Zhang Q, Guccione E, Wai LE, Koh S, Hwang W, Chow WC, Bertoletti A. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology. 2019 May;156(6):1862-1876.e9. doi: 10.1053/j.gastro.2019.01.251. Epub 2019 Jan 31.

Results Reference

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PubMed Identifier

25308176

Citation

Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.

Results Reference

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PubMed Identifier

21145860

Citation

Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.

Results Reference

background

PubMed Identifier

23941866

Citation

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.

Results Reference

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TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

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