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

Phase 1, Open-label, Two Routes IV and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-CAR T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

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.

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