An Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of ECT204 T-Cell Therapy in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-3)
Overview
- Phase
- Phase 1
- Intervention
- ECT204 T cells
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Eureka Therapeutics Inc.
- Enrollment
- 20
- Locations
- 7
- Primary Endpoint
- Assess the safety and tolerability of ECT204 in adult subjects with advanced HCC
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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.
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 ECT204 T-cell therapy in adult patients with GPC3-positive advanced hepatocellular carcinoma (HCC). ECT204 is an autologous T-cell product built on the ARTEMIS® cell receptor platform that involves two GPC3-targeting surface components: an antibody-T-cell receptor (AbTCR) and a chimeric stimulating receptor (CSR; also referred to as the co-stimulatory molecule). In this study, T cells are collected from each patient and genetically modified ex vivo to co-express the GPC3-specific AbTCR and GPC3-specific CSR, then re-administered to the patient to selectively recognize and eliminate GPC3-expressing HCC tumor cells. The protocol describes two parts: Part 1 (dose escalation) and Part 2 (expansion). Part 1: Dose Escalation Part 2: Expansion \- The initial cohort of Part 2 is defined as the "RP2D Confirmatory Cohort" 'Phase 1' is defined as Part 1 plus the initial RP2D confirmatory cohort in Part 2, and 'Phase 2' is defined as the subsequent expansion cohort in Part 2. The protocol itself does not label phases; it uses Part 1 and Part 2 terminology only. 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed HCC, that is unresectable, recurrent, and/or metastatic.
- •GPC3-positive tumor expression confirmed by immunohistochemistry (IHC).
- •For the dose-escalation cohort: ≥10-20% tumor cells, ≥2+ IHC.
- •Beginning with the RP2D confirmatory cohort: ≥ 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.
- •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).
- •Pregnant or lactating women.
- •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 systemic immunosuppressive therapy.
- •Presence of portal vein tumor thrombus (PVTT) classified as grade Vp4, or any invasion into the inferior vena cava (IVC).
- •Ascites requiring active treatment.
- •History of organ transplant.
Arms & Interventions
Dose Escalation, RP2D Confirmatory, and Expansion (Phase 1/2 Single Arm)
Dose Escalation Cohort: Patients receive a single infusion of ECT204 T cells at one of four predefined dose levels on Day 0 after conditioning. Conditioning consists of fludarabine (Flu) and cyclophosphamide (Cy). RP2D Confirmatory Cohort: Patients receive ECT204 T cells at the RP2D on Day 0 and may receive a second infusion approximately one month later. This cohort uses the same Flu/Cy conditioning as the dose-escalation cohort; no conditioning is given before the second ECT204 infusion. Expansion Cohort: Patients receive multiple ECT204 infusions at the RP2D (initial on Day 0, planned second on Day 31, and optional third or later doses). The third infusion may be administered no earlier than Day 60, and each subsequent infusion must be separated by at least 30 days. Patients receive Flu/Cy/regorafenib before the first infusion and regorafenib alone before the second and subsequent infusions.
Intervention: ECT204 T cells
Outcomes
Primary Outcomes
Assess the safety and tolerability of ECT204 in adult subjects with advanced HCC
Time Frame: 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)
Time Frame: 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 Outcomes
- 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)
- Assess the efficacy of ECT204 | Disease Control Rate(Up to 2 years)
- Assess the efficacy of ECT204 | Duration of Response(Up to 15 years)
- Assess the efficacy of ECT204 | Progression-Free Survival(Up to 15 years)
- Assess the efficacy of ECT204 | Time to Progression (TTP)(Up to 15 years)
- Assess the efficacy of ECT204 | Overall Survival(Up to 15 years)
- Characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204, in our study subject population | Peak Exposure (Cmax)(Up to 2 years)
- 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)
- 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)
- 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)