Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)

Overview

Open-label, dose escalation, multi-center, Phase I / II study to assess the safety of an autologous T-cell product (ET140203) in adult subjects with Alpha-fetoprotein (AFP)-positive/Human Leukocyte Antigen (HLA) A-2-positive advanced hepatocellular carcinoma (HCC).

Full Title of Study: “An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140203 T Cells and Determine the Recommended Phase II Dose (RP2D) in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-1)”

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: January 2023

Detailed Description

The purpose of this study is to investigate an autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140203 T cells are autologous T cells genetically modified to carry a TCR-mimic (TCRm) construct capable of mediating cell killing by targeting tumor specific intracellular antigens and addressing solid tumor therapy challenges.

Interventions

  • Biological: ET140203 autologous T cell product
    • Autologous T cells transduced with lentivirus encoding an ET140203 expression construct

Arms, Groups and Cohorts

  • Experimental: ET140203 TCells
    • 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 ET140203T 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 ET140203T 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 ET140203T 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 DLT, and secondarily on the best tumor response

Secondary Measures

  • Assess the efficacy of ET140203 T cells in adults with advanced 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 persistence of ET140203 T cells circulating in blood over time

Participating in This Clinical Trial

Inclusion Criteria

  • Histologically confirmed HCC with serum AFP >200ng/ml at time of screening and following most current line of therapy OR radiographic diagnosis of HCC with serum AFP >400ng/ml at time of screening and following most current line of therapy. – Metastatic or locally advanced, unresectable HCC – Must have failed or not tolerated at least two (2) different anti-HCC systemic agents – Molecular Human Leukocyte Antigen ("HLA") class I allele typing confirms participant carries at least one HLA-A2 allele – Life expectancy of at least 4 months – Karnofsky Performance Scale greater than or equal to 70 – At least 1 measurable lesion on imaging by RECIST – Child-Pugh A or B7 – Absolute neutrophil count greater than or equal to 1,500/mm^3 – Platelet count greater than or equal to 60,000/mm^3 Exclusion Criteria:

  • Clinically significant cardiac disease – Clinically significant pre-existing illness or active infection – Clinically significant Central Nervous System (CNS) or neural dysfunction – Active autoimmune disease requiring therapy – Active malignancy other than HCC unless expected survival is greater than or equal to three years without any treatment (exception: hormone/androgen-deprivation therapy) and without any organ involvement – History of organ transplant – Compromised circulation in portal vein, hepatic vein, or vena cava due to obstruction – Advanced HCC involving greater than one-third of the liver

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

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

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