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

Hepatocellular Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04502082
• Other study ID #: ETUS19AFPAR121
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 14, 2021
• Est. completion date: June 20, 2023

Study information

• Verified date: April 2024
• Source: Eureka Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: June 20, 2023
• Est. primary completion date: June 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Cancer
• Liver Neoplasm
• Liver Neoplasms
• Metastatic Liver Cancer

Intervention

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

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	Kansas University Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Eureka Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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