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")
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Eureka Therapeutics Inc.
- Enrollment
- 2
- Locations
- 3
- Primary Endpoint
- The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
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
Outcomes
Primary Outcomes
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
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
Secondary Outcomes
- Assess efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess the persistence of ET140202 T cells circulating in blood over time.(up to 2 years)
- Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST).(up to 2 years)
- Assess the expansion of ET140202 T cells in the blood shortly after infusion.(up to 2 years)