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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Biological/Vaccine: ET140203 autologous T-cell product Autologous T cells transduced with lentivirus encoding an ET140203 expression construct
Children's Hospital Los Angeles
Los Angeles, California, United States
RECRUITINGChildren's Hospital Orange County
Orange, California, United States
RECRUITINGUCSF Benioff Children's Hospitals
San Francisco, California, United States
RECRUITINGDana-Farber/Boston Children's Cancer and Blood Disorders Center
Boston, Massachusetts, United States
RECRUITINGIncidence rates of adverse events (AEs) after infusion of ET140203 T cells
Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion
Time frame: 28 days
Severity rates of adverse events (AEs) after infusion of ET140203 T cells
Safety of ET140203 T cells as assessed by the severity of adverse events (AEs) after infusion.
Time frame: 28 days
Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells
Tolerability of ET140203 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
Time frame: 28 days
The recommended phase 2 dose (RP2D) regimen of ET140203 T cell therapy primarily based on DLT
The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.
Time frame: Up to 2 years
Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC
Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time frame: Up to 2 years
Determine the pharmacokinetics of ET140203 T cells after infusion.
Assess the expansion and persistence of ET140203 T cells circulating in blood over time.
Time frame: Up to 2 years
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