Back to resultsStudy of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma (ET-109)
Primary Purpose
Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ET140202 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:
- Signed written informed consent obtained prior to study procedures
- Histologically confirmed HCC with serum AFP >200ng/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 one line of systemic therapy for advanced HCC
- 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 A or B7
- Absolute neutrophil count greater than or equal to 1,500/mm^3
- Platelet count greater than or equal to 30,000/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 unless expected survival is greater than or equal to three years without any treatment (exception: hormone/androgen-depravation 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 one-third of the liver
Sites / Locations
- City of Hope Medical Center
- UC Irvine
- UC Davis
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ET140202 T cells
Arm Description
ET140202 Receptor (+) T Cells
Outcomes
Primary Outcome Measures
Incidence rates of adverse events (AEs) after infusion of ET140202 T cells
Safety and tolerability of ET140202 T cells as assessed by committee review of dose limiting toxicities (DLTs) and incidence and severity of adverse events (AEs) after infusion
The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
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 efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).
As a measure of activity, overall response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).
As a measure of activity, CR rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).
As a measure of activity, PR rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST).
As a measure of activity, PFS rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST).
As a measure of activity, OS rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Assess the expansion of ET140202 T cells in the blood shortly after infusion.
The maximum (peak) expansion of ET140202 T cells in the blood post infusion will be determined.
Assess the persistence of ET140202 T cells circulating in blood over time.
The level of ET140202 T cells in blood will be determined to assess the persistence of ET140202 T cells during the treatment and follow-up phases of the study.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03998033
Brief Title
Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma
Acronym
ET-109
Official Title
An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140202 T Cells and Determine the Recommended Phase II Dose ("RP2D") in Adults With Advanced Hepatocellular Carcinoma ("HCC")
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Terminated
Why Stopped
Reallocation of resources to new HCC study.
Study Start Date
May 30, 2019 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)
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
This is a open-label, dose escalation, multi-center, Phase I / Phase II study to assess the safety of an autologous T-cell product (ET140202) in adult subjects with advanced Alpha-fetoprotein (AFP) positive/Human Leukocyte Antigen (HLA) A-2 positive Hepatocellular Carcinoma (HCC).
Detailed Description
The purpose of this study is to investigate a genetically modified autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140202 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
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ET140202 T cells
Arm Type
Experimental
Arm Description
ET140202 Receptor (+) T Cells
Intervention Type
Biological
Intervention Name(s)
ET140202 autologous T cell product
Intervention Description
Autologous T cells transduced with lentivirus encoding an ET140202 expression construct
Primary Outcome Measure Information:
Title
Incidence rates of adverse events (AEs) after infusion of ET140202 T cells
Description
Safety and tolerability of ET140202 T cells as assessed by committee review of dose limiting toxicities (DLTs) and incidence and severity of adverse events (AEs) after infusion
Time Frame
28 days
Title
The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
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 efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).
Description
As a measure of activity, overall response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).
Description
As a measure of activity, CR rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).
Description
As a measure of activity, PR rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST).
Description
As a measure of activity, PFS rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST).
Description
As a measure of activity, OS rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Time Frame
up to 2 years
Title
Assess the expansion of ET140202 T cells in the blood shortly after infusion.
Description
The maximum (peak) expansion of ET140202 T cells in the blood post infusion will be determined.
Time Frame
up to 2 years
Title
Assess the persistence of ET140202 T cells circulating in blood over time.
Description
The level of ET140202 T cells in blood will be determined to assess the persistence of ET140202 T cells during the treatment and follow-up phases of the study.
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:
Signed written informed consent obtained prior to study procedures
Histologically confirmed HCC with serum AFP >200ng/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 one line of systemic therapy for advanced HCC
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 A or B7
Absolute neutrophil count greater than or equal to 1,500/mm^3
Platelet count greater than or equal to 30,000/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 unless expected survival is greater than or equal to three years without any treatment (exception: hormone/androgen-depravation 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 one-third of the liver
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eureka Study Director
Organizational Affiliation
Eureka Therapeutics
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
Facility Name
UC Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma
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