ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

Prior treatment

• Recurrent HB who are candidates for complete surgical resection (e.g., isolated pulmonary relapse amendable to pulmonary metastasectomy).
• Received the following within one (1) week of leukapheresis or within two (2) weeks of conditioning chemotherapy: cytotoxic chemotherapy, radiation, other anti-cancer therapies (including immunotherapeutic agents), or immunosuppressive therapy. Systemic corticosteroids at doses greater than 5 mg/day of prednisone or equivalent doses of other corticosteroids within two (2) weeks prior to leukapheresis or conditioning chemotherapy or receipt of a T-cell engager (TCE) within two (2) months prior to leukapheresis or at any time as bridging therapy between leukapheresis and conditioning chemotherapy is exclusionary. (Note: Topical and inhaled corticosteroids in standard doses and physiological replacement doses of corticosteroids for adrenal insufficiency are allowed).
• Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study.

Other illness

• Pre-existing illness including heart failure, uncontrolled pulmonary disease not cancer-related, or psychiatric illness/social situation that would limit compliance with study requirements.
• Active, uncontrolled systemic bacterial, fungal, or viral infection. Subjects with Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C are eligible provided their infection is being treated and the viral load is controlled.
• Any known active malignancy (other than HB, HCN-NOS, or HCC).
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• History of organ transplant.

Other

• Pregnant or lactating women.
• Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.
• Compromised circulation in the main portal vein, hepatic vein, or vena cava due to partial or complete obstruction which, in the opinion of the Investigator, would make the subject unsuitable for the study.
• HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

• Histologically confirmed HB, HCN-NOS, or HCC with serum AFP \>100ng/mL at the time of screening and following the most recent line of therapy.
• Disease recurrence after remission following initial standard-of care (SOC) treatment (i.e., relapse) or failure of response to SOC treatment (i.e., refractory).
• Age ≥ 1 year and ≤ 21 years.
• Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele.
• Life expectancy of \> 4 months per the Investigator's opinion.
• Lansky or Karnofsky Performance Scale ≥ 70.
• For enrollment to the dose-finding cohort, subjects must have at least one (1) lesion ≥ 5 mm in diameter or two (2) or more lesions ≥ 3 mm in diameter. For the dose-expansion cohort, subjects must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Child-Pugh score of A6 or better.
• Adequate organ function.