Clinical Study of ET1402L1-CAR T Cells in AFP Expressing Hepatocellular Carcinoma

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC

The molecular target for ET1402L1-CART is alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ET1402L1-CART is a second generation (CD28/CD3ζ) chimeric antigen receptor (CAR) engineered with a human single-chain variable antibody fragments (scFv) against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-CART-cells in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Patients with lesion(s) localized in liver will be enrolled in the IA arm, with the ET1402L1-CART-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the IV arm, with the ET1402L1-CART-cells administered through intravenous infusion.

Eligibility Criteria:
Inclusion Criteria:

* AFP-expressing HCC and serum AFP \>100 ng/mL.
* Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 20 mm.
* Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
* Child-Pugh score of A or B
* Life expectancy \> 4 months
* Age at time of enrollment is ≥18 years of age.
* KPS ≥70%
* Adequate organ function as defined below:

  * A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute.
  * Patients must have a serum direct bilirubin ≤2 x ULN, ALT and AST ≤5 times the institutional upper limits of normal.
  * Ejection Fraction measured by echocardiogram or MUGA \>45% (evaluation done within 6 weeks of screening does not need to be repeated)
  * DLCO or FEV1 \>45% predicted
* Absolute neutrophil count (ANC) ≥ 1500/mm3 (10\^9/L)
* Platelet count ≥ 50,000/mm3 (10\^9/L)
* Negative serum pregnancy test for women with childbearing potential
* Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion criteria:

* Patients with decompensated cirrhosis: Child-Pugh Score C
* Patients with an organ transplantation history
* Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
* Patients with dependence on corticosteroids
* Patients with active autoimmune diseases requiring systemic immunosuppressive therapy
* Patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery
* Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
* Patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.).
* Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. Patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled.
* Patients with other uncontrolled diseases, such as active infections:

  * Acute or chronic active hepatitis B or hepatitis C.
  * HIV-infection
* Women who are pregnant