Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma

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.

• ET140202 autologous T cell product (Biological): Autologous T cells transduced with lentivirus encoding an ET140202 expression construct

Primary outcomes

• 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 outcomes

• 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 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.
• 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.

Sex: All, ages: 18 Years to any

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

• Eureka Study Director, Study director, Eureka Therapeutics