T-Cell Therapy (ECT204) in Adults With Advanced HCC (ARYA-3)

Eureka Therapeutics

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Regorafenib (STIVARGA®, BAY73-4506); Biological: ECT204 T cells

Study type: Interventional

Funder types: Industry

Identifiers

NCT04864054

ETUS20GPC3AR124

Details and patient eligibility

About

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.

Full 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).

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Arm A

Experimental group

Description:

Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion.

Treatment:

Biological: ECT204 T cells

Arm B

Experimental group

Description:

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.

Treatment:

Biological: ECT204 T cells

Drug: Regorafenib (STIVARGA®, BAY73-4506)