CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
2. Age 18 years up to the age of 75 (≤75), gender unlimited.
3. Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines.
4. BCLC stage B or C.
5. Liver function: Child-Pugh class A/B (5-9).
6. Eastern Cooperative Oncology Group (ECOG) Performance score≤1.
7. No previous antitumor therapy.
8. Life expectancy ≥ 6 months.
9. Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment.
10. Adequate organ and marrow function (within 4 weeks prior to study treatment initiation).
11. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study.
12. Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
13. Be willing to signed a written informed consent document before enrollment.

Exclusion Criteria:

1. Patients combined with HAV, HEV, HIV or other infectious diseases.
2. Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.
3. Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
4. Major organs dysfunction.
5. 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.
6. Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
7. 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.
8. Patients currently participating in other clinical trials who may violate this treatment plan and observations.
9. Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
10. 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.

主要终点：Safety evaluation: Incidence of Adverse events (AEs) · Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). · up to 60 weeks；Safety evaluation: Dose limited toxicity (DLTs) · The incidence, characteristic and severity of DLTs will be recorded and assessed. · up to 60 weeks；Safety evaluation: Maximum-tolerated dose (MTD) · MTD or clinical recommended dose will be recorded and evaluated. · up to 60 weeks；Efficacy evaluation: Objective Response Rate(ORR) · Objective clinical response will be assessed by investigators · up to 15months；Efficacy evaluation: Duration of Response(DOR) · The duration of objective response in patients will be recorded until 15months after the start of 1st cycle of treatment · up to 15months；Efficacy evaluation: Progress Free Survival(PFS) · Observation for progression-free survival (PFS) will be recorded until 15 months after the start of 1st cycle of treatment · up to 15months

• γδ T cells+ PD-1 monoclonal antibody+ targeted drugs · EXPERIMENTAL · Patients will receive 4 cycles of ex-vivo expanded allogeneic γδ T cells treatments, at three-weeks' intervals. Ex-vivo expanded γδ T cells are transfused to patients in a typical 3+3 dose-escalation design (Dose escalation, 1×10\^8/kg, 2×10\^8/kg,4×10\^8/kg).
• PD-1 monoclonal antibody+ targeted drugs · ACTIVE_COMPARATOR · PD-1 monoclonal antibody+ targeted drugs

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.