Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma

Phase 1

Terminated

• Conditions: Metastatic Liver Cancer; Liver Cancer; Liver Neoplasm; Hepatocellular Carcinoma
• Interventions: Biological: ET140202 autologous T cell product

• Registration Number: NCT03998033
• Lead Sponsor: Eureka Therapeutics Inc.

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 Timeline

• Study Start: 2019-05-30
• Study First Submitted: 2019-06-07
• Study First Submitted QC: 2019-06-24
• Study First Posted: 2019-06-25
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-19
• Last Update Posted: 2022-08-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ET140202 T cells	ET140202 autologous T cell product	ET140202 Receptor (+) T Cells

Primary Outcome Measures

Name	Time	Method
The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy	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
Incidence rates of adverse events (AEs) after infusion of ET140202 T cells	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

Secondary Outcome Measures

Name	Time	Method
Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).	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 the persistence of ET140202 T cells circulating in blood over time.	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.
Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).	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).	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).	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).	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.	up to 2 years	The maximum (peak) expansion of ET140202 T cells in the blood post infusion will be determined.

Trial Locations

Locations (3)

City of Hope Medical Center; 🇺🇸 Duarte, California, United States

UC Irvine; 🇺🇸 Irvine, California, United States

UC Davis; 🇺🇸 Sacramento, California, United States