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

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Neoplasm; Metastatic Liver Cancer
• Interventions: Biological: ECT204 T cells; Drug: Regorafenib (STIVARGA®, BAY73-4506)

• Registration Number: NCT04864054
• Lead Sponsor: Eureka Therapeutics Inc.

Brief 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.

The study includes a dose escalation phase (Part 1 or Phase I) to determine the Recommended Phase II Dose (RP2D), followed by an expansion phase (Part 2 or Phase II) to further assess safety and efficacy.

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): During the expansion phase, the initial group of patients will receive ECT204 monotherapy at the RP2D to confirm the RP2D. After confirmation of the RP2D, subsequent patients will receive pre-treatment with regorafenib (STIVARGA®) prior to 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).

Study Timeline

• Study First Submitted: 2021-04-14
• Study First Submitted QC: 2021-04-26
• Study First Posted: 2021-04-28
• Study Start: 2022-03-11
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-06
• Last Update Posted: 2025-08-12
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Histologically confirmed HCC, which is unresectable, recurrent and/or metastatic.

• GPC3-positive expression in HCC tumor cells confirmed by immunohistochemistry (IHC).

  • For Phase 1 (dose escalation): ≥10-20% tumor cells, ≥2+ IHC).
  • For Phase 2 (expansion): ≥ 50% tumor cells, 2+/3+ IHC).

• 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

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ECT204 Monotherapy Arm	ECT204 T cells	Approximately 5 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion.
Regorafenib Pre-Treatment + ECT204 Arm	ECT204 T cells	Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion. Subjects will also receive pre-treatment with regorafenib (STIVARGA®) before ECT204 administration.
Regorafenib Pre-Treatment + ECT204 Arm	Regorafenib (STIVARGA®, BAY73-4506)	Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion. Subjects will also receive pre-treatment with regorafenib (STIVARGA®) before ECT204 administration.

Primary Outcome Measures

Name	Time	Method
Assess the safety and tolerability of ECT204 in adult subjects with advanced HCC	Up to 2 years (active assessment period); additional long-term follow-up (LTFU) up to 15 years	Type, frequency, and severity of adverse events (AEs) and laboratory abnormalities
Determine the Recommended Phase II Dose (RP2D) of ECT204 (Concluded During Phase 1 of the study)	Up to 28 days	RP2D determination is based on the maximum tolerated dose (MTD), defined as the highest dose level at which the proportion of subjects experiencing a Dose-Limiting Toxicity (DLT) is less than or equal to 30% and does not exceed the maximum administered dose (MAD). Final determination is based on the observed DLT rates and manufacturing capability, and is made by the Dose Escalation Committee (DEC).

Secondary Outcome Measures

Name	Time	Method
Assess the efficacy of ECT204 in adult subjects with advanced HCC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (RECIST v1.1) as the primary criterion.	Up to 2 years	Overall Response Rate (ORR), defined as the proportion of subjects with a best overall response (BOR) of either complete response (CR) or partial response (PR).
Assess the efficacy of ECT204 | Disease Control Rate	Up to 2 years	Disease Control Rate (DCR), defined as the proportion of subjects with BOR of either CR, PR, or stable disease (SD).
Assess the efficacy of ECT204 | Duration of Response	Up to 15 years	Duration of Response (DOR), defined as the time from first response to progressive disease (PD) or death.
Assess the efficacy of ECT204 | Progression-Free Survival	Up to 15 years	Progression-Free Survival (PFS), defined as the time from ECT204 infusion to PD or death
Assess the efficacy of ECT204 | Overall Survival	Up to 15 years	Overall Survival (OS), defined as the time from ECT204 T-cell infusion to the date of death.
Characterize the pharmacokinetic (PK) profile of ECT204 will including the expansion and persistence of ECT204, in our study subject population | Peak Exposure (Cmax)	Up to 2 years	The peak exposure (Cmax) will be measured.
Characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204, in our study subject population | Partial area under the curve (pAUC)	Up to 2 years	The partial area under the curve (pAUC) will be measured.
Characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204, in our study subject population | Other relevant PK parameters in peripheral blood (PB)	Up to 2 years	Other relevant PK parameters of ECT204 in peripheral blood (PB) will be measured.
Characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204, in our study subject population | Time to reach peak exposure (Tmax)	Up to 2 years	The time to reach peak exposure (Tmax) will be measured.

Trial Locations

Locations (5)

Fred Hutchinson Cancer Center, University of Washington; 🇺🇸 Seattle, Washington, United States

City of Hope; 🇺🇸 Duarte, California, United States

Kansas University Medical Center, Principal Investigator: 🇺🇸 Westwood, Kansas, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

National Taiwan University Cancer Center; 🇨🇳 Taipei, Taiwan