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.
ECT204 is an autologous T-cell product built on the ARTEMIS® Cell Receptor platform, incorporating two GPC3-targeting surface components: an antibody-T-cell receptor (AbTCR) and a chimeric stimulating receptor (CSR). Each subject's T cells are collected and genetically modified ex vivo to co-express these receptors, then re-administered to selectively recognize and eliminate GPC3-expressing HCC tumor cells. The study consists of a completed Phase 1 and a Phase 2 expansion cohort. Phase 1 used a traditional 3+3 dose-escalation design to determine the recommended Phase 2 dose (RP2D), followed by an RP2D confirmatory cohort to further characterize safety. Phase 2 evaluates a multi-infusion strategy of up to four ECT204 infusions administered across two treatment cycles, with the second cycle administered to subjects who achieve stable disease or better at the Month 2 assessment. The active assessment period extends for 2 years (24 months) after the first ECT204 infusion (Day 0). Subjects then enter long-term follow-up (LTFU) for ongoing safety and overall survival assessments through Year 15.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
60
ECT204 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the ECT204 transgene.
City of Hope
Duarte, California, United States
RECRUITINGKansas University Medical Center, Principal Investigator:
Westwood, Kansas, United States
COMPLETEDRoswell Park Comprehensive Cancer Center
To assess the safety and tolerability of ECT204.
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.
Time frame: Up to 2 years (active assessment period); additional long-term follow-up (LTFU) up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Overall Response Rate (ORR)
ORR, defined as the proportion of subjects with a best overall response (BOR) of either CR or PR.
Time frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Duration of Response (DOR)
DOR, defined as the time from first documented occurrence of CR or PR to PD or death from any cause, whichever occurs first.
Time frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Progression-Free Survival (PFS)
PFS, defined as the time from first ECT204 infusion to PD or death from any cause, whichever occurs first.
Time frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Disease Control Rate (DCR)
DCR, defined as the proportion of subjects with BOR of CR, PR, or SD.
Time frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Time to Response (TTR)
TTR, defined as the time from first ECT204 infusion to the first documented occurrence of CR or PR, among subjects who achieve an objective response.
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Buffalo, New York, United States
Montefiore Einstein Comprehensive Cancer Center
The Bronx, New York, United States
RECRUITINGOregon Health and Sciences University
Portland, Oregon, United States
RECRUITINGUniversity of Texas Southwestern, Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, United States
RECRUITINGFred Hutchinson Cancer Center, University of Washington
Seattle, Washington, United States
RECRUITINGNational Taiwan University Cancer Center
Taipei, Taiwan
RECRUITINGTime frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Time to Progression (TTP)
TTP, defined as the time from first ECT204 infusion to PD.
Time frame: Up to 15 years
To assess the efficacy of ECT204 using RECIST v1.1 | Overall Survival (OS)
OS, defined as the time from first ECT204 infusion to death from any cause.
Time frame: Up to 15 years
To evaluate changes in serum GPC3 as a pharmacodynamic marker of ECT204 activity.
Change from baseline in serum GPC3 over time; association between dynamic changes in serum GPC3 and radiographic tumor response by RECIST v1.1.
Time frame: Up to 2 years
To characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204 | Peak exposure (Cmax)
Cmax will be determined
Time frame: Up to 2 years
To characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204 | Time to reach peak exposure (Tmax)
Tmax will be determined
Time frame: Up to 2 years
To characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204 | Area under the concentration-time curve to the last quantifiable concentration (AUCt)
AUCt will be determined
Time frame: Up to 2 years