Allogeneic Gamma-delta T Cells Combined With Targeted Therapy and Immunotherapy in a Phase 1 Clinical Trial of Hepatocellular Carcinoma Resistant to PD-1 Monoclonal Antibody

Официальное название

The Safety and Efficacy Assessment of Allogeneic γδ T Cells Combined With Targeted Therapy and Immunotherapy in Hepatocellular Carcinoma Patients

Обзор

The purpose of this study is to evaluate the safety and efficacy of allogeneic γδ T cells combined with targeted therapy and PD-1 monoclonal antibody in patients with hepatocellular carcinoma resistant to PD-1 monoclonal antibody. Hepatocellular Carcinoma

Подробное описание

This is a double-arm, single-center, randomized, open label phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus targeted therapy and PD-1 monoclonal antibody in patients with BCLC stage B or C hepatocellular carcinoma (HCC). A typical 3+3 dose-escalation design will be used to determine the optimal dose level of γδ T cells based on the incidence of dose-limiting toxicity (DLT). The initial infusion dose level will start from 1×10\^8/kg to 4×10\^8/kg in every 3 weeks.

Вмешательства

• Биопрепарат γδ T cells
  Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδ T cells from donors will be adoptively transfused.
• Препарат PD-1 monoclonal antibody
  Humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.
• Препарат targeted drugs
  Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.

Первичные конечные точки

• Safety evaluation: Incidence of Adverse events (AEs) [Срок оценки: up to 60 weeks]
• Safety evaluation: Dose limited toxicity (DLTs) [Срок оценки: up to 60 weeks]
• Efficacy evaluation: Objective Response Rate(ORR) [Срок оценки: up to 15months]
• Efficacy evaluation: Duration of Response(DOR) [Срок оценки: up to 15months]
• Efficacy evaluation: Progress Free Survival(PFS) [Срок оценки: up to 15months]
• Efficacy evaluation: Overall Survival (OS) [Срок оценки: up to 15months]

Критерии участия

Критерии включения

• Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
• Age 18 years up to the age of 75 (≤75), gender unlimited.
• Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines.
• BCLC stage B or C.
• Liver function: Child-Pugh class A/B (5-9).
• Eastern Cooperative Oncology Group (ECOG) Performance score≤1.
• Treated with standard treatment options (anti-PD-1, targeted drugs) ≥3months and experiencing progressive disease according to RECIST 1.1.
• Life expectancy ≥ 6 months.
• Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment.
• Adequate organ and marrow function (within 4 weeks prior to study treatment initiation).
• Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study.
• Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).

Be willing to signed a written informed consent document before enrollment.

Критерии исключения

• Patients combined with HAV, HEV, HIV or other infectious diseases.
• Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.
• Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
• Major organs dysfunction.
• Combined with other severe organic diseases or mental illnesses, including any uncontrolled clinically significant systematic diseases such as urinary, circulatory, respiratory, neurological, psychiatric, digestive, endocrine and immune diseases.
• Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
• Immunosuppressive or systemic cytotoxic drugs may require within 6 months prior to screening or during the study; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.
• Patients currently participating in other clinical trials who may violate this treatment plan and observations.
• Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
• Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed: patients with any serious acute or chronic physical or mental illness, or laboratory abnormalities.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06364800 · GDT-001-07-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗