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.
Conditions
Hepatoblastoma, Hepatocellular Carcinoma (HCC), Liver Neoplasms, Metastatic Liver Cancer, Liver Cancer, HEMNOS
Recruitment Status
Recruiting
Detailed Description
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.
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed HB, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of screening and following the most recent line of therapy.
Disease reoccurrence after remission following initial standard-of-care (SOC) treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory).
Age ≥ 1 year and ≤ 21 years.
Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject carries at least one HLA-A2 allele.
Life expectancy of > 4 months per Principal Investigator's opinion.
Lansky or Karnofsky Performance Scale ≥ 70.
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 RECIST v1.1.
Child-Pugh score of B7 or better.
Adequate organ function.
Exclusion Criteria:
Received the following within two (2) weeks of leukapheresis and within two (2) weeks of conditioning chemotherapy: cytotoxic chemotherapy, radiation, systemic corticosteroids, other anti-cancer therapies (including immunotherapeutic agents), or any other immunosuppressive agents (Note: use of inhaled or topical steroids is not exclusionary).
Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study.
Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide.
Active autoimmune disease requiring systemic immunosuppressive therapy.
Compromised circulation in the main portal vein, hepatic vein, or vena cava due to partial or complete obstruction which, in the opinion of the Principal Investigator, would make the subject unsuitable for the study.
History of organ transplant.
HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).
Intervention
Intervention Type
Intervention Name
Drug
ET140203 T Cells
Phase
Phase 1, Phase 2
Gender
All
Min Age
1 Year
Max Age
21 Years
Download Date
December 19, 2022
Principal Investigator
N/A
Primary Contact Information
For more information on this trial, visit clinicaltrials.gov.
Contact
For more information and to contact the study team: