t-cell therapy (ect204) in adults with advanced hcc

Conditions: Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Neoplasm; Metastatic Liver Cancer

Summary: this is an open-label, dose escalation, multi-center, phase i/ii clinical trial aimed at assessing the safety and preliminary efficacy of an investigational artemis® ect204 t-cell therapy. the trial is suitable for adult subjects (≥ 18 years of age) diagnosed with gpc3-positive hcc, who have failed or not tolerated at least two (2) different anti-hcc systemic agents. phase i has concluded and a recommended phase ii dose (rp2d) has been determined. we are now conducting phase ii to further confirm the safety profile of ect204 and evaluate its efficacy.

this is an open-label, dose escalation, multi-center, phase i/ii clinical trial. the purpose of this study is to evaluate an investigational artemis® ect204 t-cell therapy in adult patients with gpc3-positive advanced hepatocellular carcinoma (hcc). in this study, a patient's t cells are collected and genetically modified to express eureka's proprietary anti-gpc3 artemis t cell receptors (abtcr). these modified t cells are then reintroduced into the patient to specifically seek out and destroy gpc3-expressing cancer cells. phase 1 (dose escalation phase): completed; rp2d of ect204 was determined. phase 2 (expansion phase): the expansion phase includes 2 study arms. arm a: subjects will receive ect204 as monotherapy arm b: subjects will receive pre-treatment with regorafenib (stivarga®) before ect204 administration. the active assessment period of the study will continue for 2 years. subjects will be followed for assessment of treatment safety and overall survival during long term follow-up (ltfu; year 2 -15).

Eligibility criteria:
inclusion criteria: * histologically confirmed hcc, which is unresectable, recurrent and/or metastatic. * gpc3-positive expression in hcc tumor cells confirmed by immunohistochemistry (ihc). to be eligible for phase 2 (expansion phase) of the study, the subject's tumor biopsy sample (resection or needle core sample) must demonstrate that more than 50% of tumor cells exhibit at least 3+ gpc3 expression intensity. * must have failed, or not tolerated, at least two (2) different anti-hcc systemic agents. * life expectancy of at least 4 months per the investigator's opinion. * karnofsky performance scale of 70 or higher. * measurable disease by recist v1.1. previously treated lesions are allowed as long as there is a new confirmed measurable component. * child-pugh score of a6 or better. * adequate organ function. exclusion criteria: * pre-existing illness (e.g., symptomatic congestive heart failure) that would limit compliance with study requirements. * active, uncontrolled systemic bacterial, fungal, or viral infection. subjects with human immunodeficiency virus (hiv), hepatitis b, or hepatitis c are eligible provided their infection is being treated and the viral load is controlled. * active malignancy (other than hcc), with the exception of cholangiocarcinoma (cca) or any malignancy without any organ involvement and with an expected survival ≥ 3 years without any treatment (exception: hormone/androgen- deprivation therapy). * currently receiving or ending (\< 14 days from date of consent) liver tumor-directed therapy (e.g., radiation, ablation, embolization), or hepatic surgery. * concurrently receiving other investigational agents, biological, chemical, or radiation therapies, while participating in the study. * active autoimmune disease requiring therapy. * compromised circulation in the main portal vein, hepatic vein, or vena cava due to obstruction. * history of organ transplant. * advanced hcc involving greater than half (50%) of the liver.

Keywords: hepatocellular carcinoma advanced hcc late-stage hcc liver cancer liver neoplasm metastatic liver cancer metastatic hcc t-cell therapy immunotherapy hcc