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

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.

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.