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

Официальное название

Safety and Tolerability Study of Redirected HBV-Specific T Cells in Patients With Hepatitis B Virus (HBV)-Related Hepatocellular Carcinoma (SAFE-T-HBV)

Обзор

This is a single center, single arm and 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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Safety evaluation of mRNA HBV/TCR T-cell treatment [Срок оценки: Start of treatment until 28 days post last dose]
• Analysis of modifications of tumour microenvironment caused by mRNA HBV/TCR T-cell treatment [Срок оценки: Start of treatment until end of study]

Вторичные конечные точки (3)

• Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [Срок оценки: Up to 4 years]
• Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [Срок оценки: Up to 4 years]
• Evaluation of anti-tumor efficacy of mRNA HBV/TCR T-cell treatment [Срок оценки: Up to 4 years]

Критерии участия

Критерии включения

• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• 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
• Serum HBsAg positivity
• Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points)
• Life expectancy of at least 3 months
• HLA class 1 profile matching HLA-class I restriction element of the available T cell receptors (restricted by either HLA-A\*02:01 or HLA-A\*24:02).

Критерии исключения

• Brain metastasis
• Second primary malignancy that is clinically detectable at the time of consideration for study enrolment, except for in situ carcinoma of the cervix, non-melanoma skin carcinoma localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer and superficial bladder tumors
• Use of immune checkpoint inhibitors and/or tyrosine kinase inhibitor (TKI) within 5 half-lives of the drug prior to baseline liver biopsy procedure
• Alterations of concomitant medications which could potentially cause drug induced liver injury and affect liver biopsy result within 3 months of baseline liver biopsy procedure.
• Likelihood to require any immunosuppressive treatments during the period of the clinical trial.
• 7\. Last RFA/TACE treatment within 3 months prior to first LioCyx-M infusion; Last Y90 therapy treatment within 6 months prior to first dose of mRNA HBV/TCR T-cells
• Decompensated cirrhosis Child-Pugh B or C (7 - 15 points)
• Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
• Use of any investigational product (IP) or investigational medical device within 30 days of study drug administration
• Serum HBV DNA levels ≥ 200 IU/ml at screening
• Serum HBsAg levels ≥ 10,000 IU/ml at screening
• Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
• Any condition or active infections which, in the investigator's opinion, makes the subject unsuitable for trial participation
• Women who are pregnant or breast-feeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Сингапур · 1 центр

• Singapore General Hospital — Singapore

Публикации

• 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. PMID 23941866
• Kah J, Koh S, Volz T, Ceccarello E, Allweiss L, Lutgehetmann M, Bertoletti A, Dandri M. Lymphocytes transiently expressing virus-specific T cell receptors reduce hepatitis B virus infection. J Clin Invest. 2017 Aug 1;127(8):3177-3188. doi: 10.1172/JCI93024. Epub 2017 Jul 24. PMID 28737510
• 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. PMID 30711630

Идентификаторы

NCT: NCT04745403 · LTCR-HCC-3-3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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