Recruiting
Phase 1/2
ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma
Condition(s) studied
HepatoblastomaHepatocellular Carcinoma (HCC)Liver NeoplasmsMetastatic Liver CancerLiver CancerHEMNOS
Investigational drug(s) / intervention(s)
ET140203 T Cells
ET140203 T Cells: Biological/Vaccine: ET140203 autologous T-cell product
Autologous T cells transduced with lentivirus encoding an ET140203 expression construct
Study summary
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, HCN-NOS, or HCC.
Eligibility
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 recurrence 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 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).
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).
Primary outcome measure(s)
- Incidence rates of adverse events (AEs) after infusion of ET140203 T cells — 28 days
Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion
- Severity rates of adverse events (AEs) after infusion of ET140203 T cells — 28 days
Safety of ET140203 T cells as assessed by the severity of adverse events (AEs) after infusion.
- Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells — 28 days
Tolerability of ET140203 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
- The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT — Up to 2 years
The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.
Trial sites (4)
| Facility | City | Region | Status |
| Children's Hospital Los Angeles |
Los Angeles |
California |
Recruiting |
| Children's Hospital Orange County |
Orange |
California |
Recruiting |
| UCSF Benioff Children's Hospitals |
San Francisco |
California |
Recruiting |
| Dana-Farber/Boston Children's Cancer and Blood Disorders Center |
Boston |
Massachusetts |
Recruiting |
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