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出境医 / 临床实验 / Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma (ET-109)

Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma (ET-109)

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).

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Liver Cancer Liver Neoplasm Metastatic Liver Cancer Biological: ET140202 autologous T cell product Phase 1 Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Sequential 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 ET140202 T Cells and Determine the Recommended Phase II Dose ("RP2D") in Adults With Advanced Hepatocellular Carcinoma ("HCC")
Actual Study Start Date : May 30, 2019
Actual Primary Completion Date : December 31, 2020
Actual Study Completion Date : December 31, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: ET140202 T cells
ET140202 Receptor (+) T Cells
 Biological: ET140202 autologous T cell product
Autologous T cells transduced with lentivirus encoding an ET140202 expression construct
Outcome Measures
Primary Outcome Measures :
  1. Incidence rates of adverse events (AEs) after infusion of ET140202 T cells [ Time Frame: 28 days ]
    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

  2. The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy [ Time Frame: 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 :
  1. Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    As a measure of activity, overall response rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  2. Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    As a measure of activity, CR rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  3. Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    As a measure of activity, PR rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  4. Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    As a measure of activity, PFS rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  5. Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    As a measure of activity, OS rate will be assessed by radiographic scans and assessed according to RECIST criteria.

  6. Assess the expansion of ET140202 T cells in the blood shortly after infusion. [ Time Frame: up to 2 years ]
    The maximum (peak) expansion of ET140202 T cells in the blood post infusion will be determined.

  7. Assess the persistence of ET140202 T cells circulating in blood over time. [ Time Frame: up to 2 years ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
UC Irvine
Irvine, California, United States, 92697
UC Davis
Sacramento, California, United States, 95817
Sponsors and Collaborators
Eureka Therapeutics Inc.
Investigators
Layout table for investigator information
Study Director: Eureka Study Director Eureka Therapeutics
Tracking Information
First Submitted Date  ICMJE June 7, 2019
First Posted Date  ICMJE June 25, 2019
Last Update Posted Date April 19, 2021
Actual Study Start Date  ICMJE May 30, 2019
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Incidence rates of adverse events (AEs) after infusion of ET140202 T cells [ Time Frame: 28 days ]
    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 [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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. [ Time Frame: up to 2 years ]
    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. [ Time Frame: up to 2 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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). [ Time Frame: up to 2 years ]
    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 circulating in blood over time [ Time Frame: up to 2 years ]
    The level of ET140202 T cells in blood will be determined to assess the expansion of ET140202 T cells during the treatment and follow-up phases of the study.
  • Assess the persistence of ET140202 T cells circulating in blood over time [ Time Frame: up to 2 years ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma
Official Title  ICMJE 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")
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatocellular Carcinoma
  • Liver Cancer
  • Liver Neoplasm
  • Metastatic Liver Cancer
Intervention  ICMJE Biological: ET140202 autologous T cell product
Autologous T cells transduced with lentivirus encoding an ET140202 expression construct
Study Arms  ICMJE Experimental: ET140202 T cells
ET140202 Receptor (+) T Cells
Intervention: Biological: ET140202 autologous T cell product
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 12, 2021) 		2
Original Estimated Enrollment  ICMJE
 (submitted: June 24, 2019) 		50
Actual Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03998033
Other Study ID Numbers  ICMJE ETUS18AFPAR109
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eureka Therapeutics Inc.
Study Sponsor  ICMJE Eureka Therapeutics Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Eureka Study Director Eureka Therapeutics
PRS Account Eureka Therapeutics Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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