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

Sponsor

Eureka Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04502082

Collaborator

(none)

Enrollment

Locations

Arm

25.6

Anticipated Duration (Months)

12.5

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma Liver Cancer Liver Neoplasm Metastatic Liver Cancer	Biological: ET140203 autologous T cell product	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Sequential AssignmentSequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Apr 14, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Incidence rates of adverse events (AEs) after infusion of ET140203 T cells [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 [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 [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 [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 Outcome Measures

Assess the efficacy of ET140203 T cells in adults with advanced HCC. [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. [up to 2 years]
Assess the persistence of ET140203 T cells circulating in blood over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010
2	UC Irvine	Irvine	California	United States	92697
3	UC Davis	Sacramento	California	United States	95817
4	Kansas University Medical Center	Westwood	Kansas	United States	66205