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.
The trial starts with a dose escalation phase. A traditional dose escalation model (3+3) design will be used to determine the recommended phase II dose (RP2D). Subjects will then be treated at the RP2D in the expansion phase of the trial. Following treatment, tumor response assessments will be performed at Months 1, 3, 6, 9, 12, 18, and 24. At each tumor response assessment visit, imaging will be performed (triphasic CT Scan) and used for response evaluation. Serum AFP levels will also be measured at each tumor response assessment visit. The active assessment phase of the study will continue for 2 years. Subjects will be followed for 15 years post-treatment for assessment of treatment safety and overall survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Biological/Vaccine: ET140203 autologous T-cell product Autologous T cells transduced with lentivirus encoding an ET140203 expression construct
UCSF 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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