Title: Single-center, open clinical study on the efficacy and safety of c-Met/PD-L1 CAR-T
      cell injection in the treatment of primary hepatocellular carcinoma

      Research purpose:

      Primary outcome:

      To evaluate the efficacy of c-Met/PD-L1 CAR-T cell injection in the treatment of primary
      hepatocellular carcinoma.

      Secondary purpose:

        1. To evaluate the clinical safety of c-Met/PD-L1 CAR-T cell injection in the treatment of
           primary hepatocellular carcinoma;

        2. To assess the amplification and persistence of c-Met/PD-L1 CAR-T cells in subjects.

      Study design:Single center, open clinical study

      Subjects:Patients with primary hepatocellular carcinoma

      Clinical trial cycle:

      Screening stage:Selecting enrolled patients and collecting peripheral mononuclear cells;
      Treating stage: Pretreating and the backtransfusing c-Met/PD-L1 CAR-T cells Follow-up
      stage:Treatment was observed for 28 days (short-term follow-up), 28 days to 24 weeks
      (mid-term follow-up), and 24 weeks to progression/death (long-term follow-up);

      Trial product:

      Trial product:c-Met/PD-L1 CAR-T cells Dosage:The backtransfusion dose was determined by the
      investigator based on the subject's own/disease condition and in vitro preparation
      (recommended dose: 2 * 10^6/kg); Infusion way:Steady intravenous drip within 15 to 30 minutes

      Clinical trial procedure:

        1. The screening period:

           The subjects signed the informed consent form and performed a series of examinations
           according to the interview flow chart. The researchers judged whether the subjects met
           the inclusion criteria according to the examination results and inclusion/exclusion
           criteria, and did not meet the exclusion criteria. If the subjects were enrolled,
           peripheral blood mononuclear cells were collected, and the collection standard was 2-4 *
           10^8 white blood cells;

        2. nonmyeloablative pretreatment:(The following options are selected on a case-by-case
           basis)

             1. Fludarabine+Cyclophosphamide (FC)

             2. Bis-1-nitrosourea+Etoposide+Arabinoside+Cyclophosphamide (BECA);

        3. Retransfusion period:

           The specific time and dose of retransfusion can be determined by the researchers;

        4. Short-term follow-up period:

           Subjects will undergo a series of examinations according to the visit flow chart within
           28 days after the expected dose of c-Met/PD-L1 CAR-T cells injection.The short-term
           efficacy and safety of c-Met/PD-L1 CAR-T cells injection were evaluated by the
           researchers based on the test results.

        5. Mid-term follow-up:

           Subjects will undergo a series of examinations according to the visit flow chart 28 days
           to 24 weeks after re-transfusion of c-Met/PD-L1 CAR-T cells injection.The researchers
           will evaluate the mid-term efficacy and safety of c-Met/PD-L1 CAR-T cells based on the
           test results.

        6. Long-term follow-up:

           Subjects will undergo a series of examinations according to the visit flow chart 24
           weeks later until progress or death after retransfusion of c-Met/PD-L1 CAR-T cells.The
           long-term efficacy and safety of c-Met/PD-L1 CAR-T cells will be evaluated according to
           the test results.

        7. Withdrawal visit (at any time) :All subjects may withdraw from this study at any stage
           of the trial.If the subjects withdraw from the study after returning to the c-Met/PD-L1
           CAR-T cells, they shall complete the inspection items required in the visit flow chart,
           and the reason for the withdrawal shall be recorded in detail by the researchers.If the
           subject passes screening but withdraws from the visit before returning to the
           c-Met/PD-L1 CAR-T cells, only the baseline and screening tests need to be completed, and
           the reason for withdrawal will be recorded in detail by the investigators.If the subject
           withdraws from the screening test before the end of the screening test, only the
           screening test shall be completed and the reason for withdrawal shall be recorded in
           detail by the investigators.If treatment is discontinued due to adverse reactions (AE),
           the investigators will follow up with the necessary safety until the subjects return to
           baseline or to a stable state.

      Evaluation index Main evaluation index

        1. Objective tumor remission rate (ORR),complete remission (CR) and partial remission (PR)
           at 4 weeks, 12 weeks, 24 weeks and 48 weeks after treatment with c-Met/PD-L1 CAR-T
           cells;

        2. Overall survival

        3. Progression free survival

        4. Event-free survival

      Secondary evaluation index

        1. Incidence of treatment-related adverse events (level 3 or level 4 adverse reactions,
           CTCAE V4.03 criteria). These included adverse events related to the treatment of
           c-Met/PD-L1 CAR-T cells, severe adverse events and clinically significant laboratory
           abnormalities;

        2. The amplification level of c-Met/PD-L1 CAR-T cells in the subjects varied with time;

        3. Duration of c-Met/PD-L1 CAR-T cells in the subjects;

        4. The abatement features of hepatocellular carcinoma in subjects.

      Statistical analysis SPSS18.0 was used for statistical analysis

        1. The primary and secondary end points were analyzed by intentionality. The statistical
           analysis method of the end point was used to describe tumor ORR according to different
           follow-up time. Kaplan-meier method and survival curve were used to describe OS, PFS and
           EFS

        2. The statistical analysis method of the secondary study endpoint was to describe the
           occurrence number and incidence of treatment-related adverse events, and to compare the
           difference of vital signs and laboratory indexes before and after treatment