T-Cell Therapy (ECT204) in Adults With Advanced HCC
Purpose
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.
Conditions
- Hepatocellular Carcinoma
- Liver Cancer, Adult
- Liver Neoplasm
- Metastatic Liver Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- In Phase 2 (expansion phase) of the Phase I/II study, subjects will be assigned in a parallel, non-randomized manner to one of two expansion cohorts: Arm A or Arm B.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm A |
Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion. |
|
|
Experimental Arm B |
Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion. Arm B subjects will also receive pre-treatment with regorafenib (STIVARGA®) before ECT204 administration. |
|
Recruiting Locations
Westwood, Kansas 66205
More Details
- Status
- Recruiting
- Sponsor
- Eureka Therapeutics Inc.
Detailed Description
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).