An Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of ET140203 T Cells in Pediatric Subjects with Relapsed/Refractory Hepatoblastoma (HB), Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), or Hepatocellular Carcinoma (HCC)

Protocol # :
Hepatocellular Carcinoma (HCC)
Liver Neoplasms
Metastatic Liver Cancer
Liver Cancer
Disease Sites
Principal Investigator
O'Neill, Allison, F.

Trial Description

Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the
safety/tolerability and determine the recommended Phase II Dose (RP2D) of ET140203 T-cells in
pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB,

Eligibility Requirements

Inclusion Criteria:

1. 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.

2. Disease reoccurrence after remission following initial standard-of care (SOC)
treatment (i.e., relapse) or failure of response to SOC treatment (i.e., refractory).

3. Age ≥ 1 year and ≤ 21 years.

4. Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject
carries at least one HLA-A2 allele.

5. Life expectancy of > 4 months per the Investigator's opinion.

6. Lansky or Karnofsky Performance Scale ≥ 70.

7. 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.

8. Child-Pugh score of A6 or better.

9. Adequate organ function.

Exclusion Criteria:

1. Recurrent HB who are candidates for complete surgical resection (e.g., isolated
pulmonary relapse amendable to pulmonary metastasectomy).

2. Pre-existing illness including heart failure, uncontrolled pulmonary disease not
cancer-related, or psychiatric illness/social situation that would limit compliance
with study requirements.

3. 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.

4. Any known active malignancy (other than HB, HCN-NOS, or HCC).

5. Pregnant or lactating women.

6. Received the following within two (2) weeks of leukapheresis or within two (2) weeks
of conditioning chemotherapy: cytotoxic chemotherapy, radiation, other anti-cancer
therapies (including immunotherapeutic agents), immunosuppressive therapy, or systemic
corticosteroids at doses greater than 5 mg/day of prednisone or equivalent doses of
other corticosteroids. (Note: Topical and inhaled corticosteroids in standard doses
and physiological replacement doses of corticosteroids for adrenal insufficiency are

7. Concurrently receiving other investigational agents, biological, chemical, or
radiation therapies, while participating in the study.

8. Contraindication for receipt of conditioning chemotherapeutic agents including
Fludarabine and Cyclophosphamide.

9. Active autoimmune disease requiring systemic immunosuppressive therapy.

10. 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.

11. History of organ transplant.

12. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).