ET1402L1-ARTEMIS™2 T Cells in Alpha Fetoprotein (AFP) Expressing Hepatocellular Carcinoma

Phase 1, Open-label, Three Routes IV, Intratumoral Injections and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-ARTEMIS™2™ T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

Clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of ET1402L1-ARTEMIS™2 T cells in patients with alpha fetoprotein positive (AFP+ ) hepatocellular carcinoma (HCC).

The molecular target for ET1402L1-ARTEMIS™2 is human leukocyte antigen (HLA) -A02 complexed with a HLA-A02-restricted peptide of alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ARTEMIS™2 is a second generation ARTEMIS™ receptor engineered with a human antibody domain against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-ARTEMIS™2 T-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 intra-hepatic artery (IA) arm or Intratumoral Injections arm, with the ET1402L1-ARTEMIS™2 T-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the intravenous (IV) arm, with the ET1402L1-ARTEMIS™2 T-cells administered through intravenous infusion.

Inclusion Criteria:

• AFP-expressing HCC and serum AFP >100 ng/mL.

• Abandon or failure in first or second line treatment

• Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele

• Child-Pugh score of A or B, Barcelona Clinic Liver Cancer stage of C or D

• Life expectancy > 4 months

• Karnofsky score ≥70%

• Adequate organ function as defined below:

  1. Patients must have a serum Total bilirubin ≤2 x Upper Limit of Normal (ULN), Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤5 times the institutional ULN.
  2. A pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute
  3. Ejection fraction measured by echocardiogram or Multiple gated acquisition scanning (MUGA) >45% (evaluation done with 6 weeks of screening does not need to be repeated)
  4. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1)>45% predicted
  5. Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
  6. Platelet count ≥ 50,000/mm3 (10^9/L)

• 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 tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
• Patients with an organ transplantation history
• 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)
• 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.
• Women who are pregnant or breast-feed
• HIV-infection