Clinical trial NCT03998033: Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma
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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Eureka Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-25
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence rates of adverse events (AEs) after infusion of ET140202 T cells
timeFrame: 28 days
measure: The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
timeFrame: up to 2 years
Secondary outcomes:
measure: Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).
timeFrame: up to 2 years
measure: Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).
timeFrame: up to 2 years
measure: Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).
timeFrame: up to 2 years
measure: Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST).
timeFrame: up to 2 years
measure: Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST).
timeFrame: up to 2 years
measure: Assess the expansion of ET140202 T cells in the blood shortly after infusion.
timeFrame: up to 2 years
measure: Assess the persistence of ET140202 T cells circulating in blood over time.
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
Study officials:
affiliation: Eureka Therapeutics
name: Eureka Study Director
role: STUDY_DIRECTOR
References: