ET140203 T Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

Overview

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.

Full Title of Study: “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)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 28, 2023

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.

Interventions

  • Drug: ET140203 T Cells
    • Biological/Vaccine: ET140203 autologous T-cell product Autologous T cells transduced with lentivirus encoding an ET140203 expression construct

Arms, Groups and Cohorts

  • Experimental: ET140203 T Cells
    • ET140203 T Cells

Clinical Trial Outcome Measures

Primary Measures

  • Incidence rates of adverse events (AEs) after infusion of ET140203 T cells
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: Up to 2 years
    • The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLTs.

Secondary Measures

  • Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC
    • Time Frame: Up to 2 years
    • Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
  • Determine the pharmacokinetics of ET140203 T cells after infusion.
    • Time Frame: Up to 2 years
    • Assess the expansion and persistence of ET140203 T cells circulating in blood over time.

Participating in This Clinical Trial

Inclusion Criteria

1. 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. 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 Principal 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 RECIST v1.1. 8. Child-Pugh score of B7 or better. 9. Adequate organ function. Exclusion Criteria:

1. 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). 2. Concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study. 3. Contraindication for receipt of conditioning chemotherapeutic agents including Fludarabine and Cyclophosphamide. 4. Active autoimmune disease requiring systemic immunosuppressive therapy. 5. 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. 6. History of organ transplant. 7. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).

Gender Eligibility: All

Minimum Age: 1 Year

Maximum Age: 21 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Eureka Therapeutics Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Pei Wang, PhD, Study Director, Eureka Therapeutics Inc.
  • Overall Contact(s)
    • Karen B Cravotto, 510-722 8719, karen.cravotto@eurekainc.com

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