ET140203 T Cells for treating pediatric liver cancer

An Open-Label, Dose Escalation, 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)

This study is testing a new type of T-cell treatment for kids with certain types of liver cancer to see if it is safe and helps them feel better.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 1 Year to 21 Years
• Sex: All
• Sponsor: Eureka Therapeutics Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, Cyclophosphamide, Fludarabine, prednisone
• Locations: 2 sites (San Francisco, California and 1 other locations)
• Trial ID: NCT04634357 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, dose escalation study designed to evaluate the safety and tolerability of ET140203 T-cells in pediatric patients with relapsed or refractory hepatoblastoma, hepatocellular neoplasm-not otherwise specified, or hepatocellular carcinoma. The trial will begin with a dose escalation phase using a traditional 3+3 design to determine the recommended Phase II dose. Following this, subjects will receive treatment at the recommended dose, with tumor response assessments conducted at regular intervals over a two-year period. Participants will be monitored for safety and overall survival for up to 15 years post-treatment.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 1 to 21 years with specific liver cancers who have experienced relapse or refractory disease.

Not a fit: Patients with liver cancer who do not meet the eligibility criteria or have a Child-Pugh score worse than A6 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for pediatric patients with difficult-to-treat liver cancers.

How similar studies have performed: While this approach is novel in the pediatric population for these specific liver cancers, similar immunotherapy strategies have shown promise in other cancer types.

Eligibility criteria

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 allowed).
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).

Where this trial is running

San Francisco, California and 1 other locations

• UCSF Benioff Children's Hospitals — San Francisco, California, United States (Recruiting)
• Dana-Farber/Boston Children's Cancer and Blood Disorders Center — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Teresa Klask, MBA

Conditions Hepatoblastoma; Hepatocellular Carcinoma; Liver Neoplasms; Metastatic Liver Cancer; Liver Cancer; HEMNOS; Relapsed/Refractory Hepatoblastoma; Pediatric