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

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")

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).

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Liver Neoplasm; Liver Cancer; Metastatic Liver Cancer
• Intervention / Treatment: Biological: ET140202 autologous T cell product

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: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Irvine, California, United States, 92697
      • UC Irvine
    • Sacramento, California, United States, 95817
      • UC Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Eureka Therapeutics Inc.
• Investigators: Study Director: Eureka Study Director, Eureka Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: August 19, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; Immunotherapy; Liver Cancer; Advanced HCC; T-cell therapy; Metastatic Liver Cancer; Late-Stage HCC; Liver Neoplasm; Metastatic HCC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: ETUS18AFPAR109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No