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

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)

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).

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Liver Neoplasm; Liver Cancer; Metastatic Liver Cancer
• Intervention / Treatment: Biological: ET140203 autologous T cell product

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.

The trial was intended to be a Phase 1/2 trial, but the sponsor terminated the trial prior to moving to Phase 2 to direct their efforts to the pediatric study (ARYA-2) for this product.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Kansas University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed HCC with serum AFP >100ng/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 A6 or better
• Absolute neutrophil count greater than or equal to 1,500/mm^3
• Platelet count greater than or equal to 75,000/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 with the exception of cholangiocarcinoma (CCA) or any malignancy with an expected survival ≥ 3 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 50% of the liver

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ET140203 TCells; ET140203 T Cells	Biological: ET140203 autologous T cell product; Autologous T cells transduced with lentivirus encoding an ET140203 expression construct

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rates of adverse events (AEs) after infusion of ET140203 T cells	Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion	28 days
Severity rates of adverse events (AEs) after infusion of ET140203 T cells	Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.	28 days
Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells	Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)	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 DLT, and secondarily on the best tumor response	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the efficacy of ET140203 T cells in adults with advanced HCC.	Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.	up to 2 years
Determine the pharmacokinetics of ET140203 T cells after infusion.	Assess the persistence of ET140203 T cells circulating in blood over time	up to 2 years

Collaborators and Investigators

• Sponsor: Eureka Therapeutics Inc.
• Investigators: Study Director: Pei Wang, PhD, Eureka Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 1, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Liver Cancer; Advanced HCC; T-cell therapy; Metastatic Liver Cancer; Hepatocellular Carcinoma HCC; Late-Stage HCC; Liver Neoplasm; Metastatic HCC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: ETUS19AFPAR121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No