T-Cell Therapy (ECT204) in Adults With Advanced HCC

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.