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

This is an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of intravenous (IV) administration of ET140203 T cells and determine the recommended Phase II dose (RP2D) of ET140203 T-cell therapy in pediatric subjects (age ≥ 1 year and ≤ 21 years) who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

A traditional dose escalation model (3+3 design) will be used to determine the RP2D, and once determined, the expansion phase will commence. A statistically relevant number of subjects will be treated at the RP2D in the expansion phase to adequately assess the therapeutic benefits and risks of ET140203 T-cell therapy. Tumor response assessments will be performed prior to 1st infusion (baseline) and at Months 1, 3, 6, 9, 12, 18, and 24. At each tumor response assessment visit, radiographic imaging will be performed and used for response evaluation. Serum AFP levels will also be measured at each tumor response assessment visit.

The active assessment period of the study will continue for 2 years. Subjects will be followed for assessment of treatment safety and overall survival during long-term follow-up (LTFU; Year 2-15).

Inclusion criteria

• 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.

Exclusion criteria

• Recurrent HB who are candidates for complete surgical resection (e.g., isolated pulmonary relapse amendable to pulmonary metastasectomy).
• 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).
• Pregnant or lactating women.
• 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.
• Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• 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.
• History of organ transplant.
• HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).