Hepatocellular CarcinomaLiver Cancer, AdultLiver NeoplasmMetastatic Liver Cancer
Investigational drug(s) / intervention(s)
ECT204 T cells
ECT204 T cells: ECT204 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the ECT204 transgene.
Study summary
This is an open-label, multi-center, Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of ECT204, an investigational ARTEMIS® T-cell therapy, in adult subjects with GPC3-positive hepatocellular carcinoma (HCC) who have experienced disease progression on, or intolerance to, prior systemic therapy.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 received at least first-line systemic therapy for HCC and have experienced disease progression on, or intolerance to, that therapy.
* Life expectancy of at least 4 months per the Investigator's opinion.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* 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.
* History of malignancy other than HCC within 5 years before screening, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other malignancies with low risk of recurrence.
* Known brain metastases or other active central nervous system (CNS) involvement, including leptomeningeal disease. Subjects with brain metastases that have been adequately treated (no evident neurological deficit and no steroid or anti-epileptic therapy for brain metastases) are eligible.
* 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), except for subjects with IVC invasion who have been treated and radiographically stable for at least 6 months prior to screening.
* Ascites requiring active treatment, such as a requirement for paracentesis or escalation of diuretic doses. Exception: Subjects maintained on a stable dose of diuretics with controlled, asymptomatic ascites are eligible.
* Active gastrointestinal (GI) bleeding event ≥ Grade 3 per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE), version 5.0, within 6 months prior to screening.
* Coagulation abnormality defined as international normalized ratio (INR) \> 1.7, unless the elevation is due to therapeutic anticoagulation that, in the Investigator's judgment, can be safely managed in the context of study procedures.
* History of organ transplant.
* HCC involving greater than 50% of the liver volume.
* Experienced allergies to any component of the study drug (ECT204), mouse immunoglobulin, or iron-dextran, or have a history of severe hypersensitivity, including anaphylaxis.
* Previously received other gene therapy (e.g., chimeric antigen receptor T-cell \[CAR-T\] therapy); exception: prior oncolytic virus therapy is permitted.).
* Contraindication for undergoing leukapheresis procedure or receipt of conditioning agents
Primary outcome measure(s)
To assess the safety and tolerability of ECT204. — 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), including treatment-emergent AEs (TEAEs), treatment-related AEs (TRAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), clinically significant laboratory abnormalities recorded as AEs, and AEs leading to permanent discontinuation.
Trial sites (8)
Facility
City
Region
Status
City of Hope
Duarte
California
Recruiting
Kansas University Medical Center, Principal Investigator:
Westwood
Kansas
Completed
Roswell Park Comprehensive Cancer Center
Buffalo
New York
Completed
Montefiore Einstein Comprehensive Cancer Center
The Bronx
New York
Recruiting
Oregon Health and Sciences University
Portland
Oregon
Recruiting
University of Texas Southwestern, Harold C. Simmons Comprehensive Cancer Center
Dallas
Texas
Recruiting
Fred Hutchinson Cancer Center, University of Washington
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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