Overview
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.
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).
Eligibility
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 v1.1.
- 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.
- Advanced HCC involving greater than half (50%) of the liver.
