Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, Metastatic Liver Cancer
Conditions
Keywords
Hepatocellular Carcinoma, HCC, Advanced HCC, Late-Stage HCC, Liver Cancer, Liver Neoplasm, Metastatic Liver Cancer, Metastatic HCC, T-cell therapy, Immunotherapy
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.
Interventions
BIOLOGICALET140202 autologous T cell product
Autologous T cells transduced with lentivirus encoding an ET140202 expression construct
Sponsors
Eureka Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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 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. |
Countries
United States
Outcome results
None listed