Clinical trial NCT04502082: Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Liver Cancer
Liver Neoplasm
Metastatic Liver Cancer
Keywords: Hepatocellular Carcinoma HCC
Advanced HCC
Late-Stage HCC
Liver Cancer
Liver Neoplasm
Metastatic Liver Cancer
Metastatic HCC
T-cell therapy
Immunotherapy
Lead sponsor: Eureka Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Sequential Assignment
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence rates of adverse events (AEs) after infusion of ET140203 T cells
timeFrame: 28 days
measure: Severity rates of adverse events (AEs) after infusion of ET140203 T cells
timeFrame: 28 days
measure: Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells
timeFrame: 28 days
measure: The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT
timeFrame: up to 2 years
Secondary outcomes:
measure: Assess the efficacy of ET140203 T cells in adults with advanced HCC.
timeFrame: up to 2 years
measure: Determine the pharmacokinetics of ET140203 T cells after infusion.
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Westwood
country: United States
facility: Kansas University Medical Center
state: Kansas
Study officials:
affiliation: Eureka Therapeutics Inc.
name: Pei Wang, PhD
role: STUDY_DIRECTOR
References: