Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)
Primary Purpose
Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ET140203 autologous T cell product
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma HCC, Advanced HCC, Late-Stage HCC, Liver Cancer, Liver Neoplasm, Metastatic Liver Cancer, Metastatic HCC, T-cell therapy, Immunotherapy
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
Sites / Locations
- City of Hope Medical CenterRecruiting
- Kansas University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ET140203 TCells
Arm Description
ET140203 T Cells
Outcomes
Primary Outcome Measures
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
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.
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)
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
Secondary Outcome Measures
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.
Determine the pharmacokinetics of ET140203 T cells after infusion.
Assess the persistence of ET140203 T cells circulating in blood over time
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04502082
Brief Title
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
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 14, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eureka Therapeutics Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ET140203 TCells
Arm Type
Experimental
Arm Description
ET140203 T Cells
Intervention Type
Biological
Intervention Name(s)
ET140203 autologous T cell product
Intervention Description
Autologous T cells transduced with lentivirus encoding an ET140203 expression construct
Primary Outcome Measure Information:
Title
Incidence rates of adverse events (AEs) after infusion of ET140203 T cells
Description
Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion
Time Frame
28 days
Title
Severity rates of adverse events (AEs) after infusion of ET140203 T cells
Description
Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.
Time Frame
28 days
Title
Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells
Description
Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
Time Frame
28 days
Title
The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT
Description
The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response
Time Frame
up to 2 years
Secondary Outcome Measure Information:
Title
Assess the efficacy of ET140203 T cells in adults with advanced HCC.
Description
Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Determine the pharmacokinetics of ET140203 T cells after infusion.
Description
Assess the persistence of ET140203 T cells circulating in blood over time
Time Frame
up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Teresa Klask, BS
Phone
510-722-8719
Ext
412
Email
Teresa.Klask@eurekainc.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pei Wang, PhD
Phone
510-972-1252
Email
Pei.Wang@eurekainc.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pei Wang, PhD
Organizational Affiliation
Eureka Therapeutics Inc.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia Aceves (Clinical Research Coordinator)
Phone
626-218-5114
Email
CAceves@coh.org
First Name & Middle Initial & Last Name & Degree
Daneng Li, MD
Facility Name
Kansas University Medical Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna Davis
Phone
913-588-0242
Email
adavis43@kumc.edu
First Name & Middle Initial & Last Name & Degree
Raed Al-Rajabi, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)
We'll reach out to this number within 24 hrs