Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— 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")

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03998033
• Other study ID #: ETUS18AFPAR109
• Status: Terminated
• Phase: Phase 1
• Start date: May 30, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: August 2022
• Source: Eureka Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Cancer
• Liver Neoplasm
• Liver Neoplasms
• Metastatic Liver Cancer

Intervention

Biological:
• ET140202 autologous T cell product
Autologous T cells transduced with lentivirus encoding an ET140202 expression construct

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California
United States	UC Irvine	Irvine	California
United States	UC Davis	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Eureka Therapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	28 days
Primary	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	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years