Allogeneic Gamma-delta T Cells Combined With Targeted Therapy and Immunotherapy in a Phase 1 Clinical Trial for First-line Treatment of Hepatocellular Carcinoma

Official title

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

Overview

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 first-line treatment of patients with hepatocellular carcinoma.

Detailed description

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.

Interventions

• Biological 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.
• Drug Targeted drugs
  Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.
• Drug 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.

Primary outcome measures

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

Eligibility criteria

Inclusion criteria

• 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.
• No previous antitumor therapy.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06364787 · GDT-001-07-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗