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

• ClinicalTrials.gov Identifier: NCT04864054
• Recruitment Status: Recruiting
• First Posted: April 28, 2021
• Last Update Posted: May 6, 2024
• Sponsor: Eureka Therapeutics Inc.
• Information provided by (Responsible Party): Eureka Therapeutics Inc.

Study Description

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.

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.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Neoplasm; Metastatic Liver Cancer	Biological: ECT204 T cells; Drug: Regorafenib (STIVARGA®, BAY73-4506)	Phase 2

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 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: In Phase 2 (expansion phase) of the Phase I/II study, subjects will be assigned in a parallel, non-randomized manner to one of two expansion cohorts: Arm A or Arm B.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: March 11, 2022
• Estimated Primary Completion Date: December 31, 2026
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; Approximately 10-15 subjects will receive ECT204 at the RP2D by intravenous infusion and preceded by cyclophosphamide and fludarabine chemotherapy for lymphodepletion.	Biological: 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.
Experimental: Arm B; 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.	Biological: 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.; Drug: Regorafenib (STIVARGA®, BAY73-4506); Regorafenib pretreatment before an ECT204 infusion.

Outcome Measures

Primary Outcome Measures :

1. To assess the safety and tolerability of ECT204 in adult subjects with advanced HCC [ Time Frame: 28 days ]
   The incidence rates of dose limiting toxicities (DLTs) and the type, frequency, and severity of adverse events (AEs) and laboratory abnormalities will be assessed by the number and severity rates after infusion of ECT204.
2. To determine the Recommended Phase II Dose (RP2D) of ECT204 (Concluded During Phase 1 of the study) [ Time Frame: 21 months - This outcome was completed on December 20, 2023 ]
   The RP2D was determined by the study Dose Escalation Committee (DEC) and chosen based on the maximum tolerated dose (MTD) that did not exceed the MTD and the maximum administered dose (MAD). The RP2D was also based on the manufacturing capability.

Secondary Outcome Measures :

1. To 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. [ Time Frame: Up to 2 years ]

   The response rate will be assessed by radiographic scans and assessed according to RECIST version 1.1. based upon the following:

   • Overall Response Rate (ORR), defined as the proportion of subjects with a best overall response (BOR) of either complete response (CR) or partial response (PR).
   • Disease Control Rate (DCR), defined as the proportion of subjects with BOR of either CR, PR, or stable disease (SD).
   • Duration of Response (DOR), defined as the time from first response to progressive disease (PD) or death.
   • Progression-Free Survival (PFS), defined as the time from ECT204 infusion to PD or death.
   • Overall Survival (OS), defined as the time from ECT204 T-cell infusion to the date of death.
2. To characterize the pharmacokinetic (PK) profile of ECT204, including the expansion and persistence of ECT204, in our study subject population [ Time Frame: Up to 2 years ]
   The peak exposure (Cmax), time to reach peak exposure (Tmax), partial area under the curve (pAUC) and other relevant PK parameters of ECT204 in peripheral blood (PB) will be measured.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Teresa Klask, MBA; 925-949-9314; Teresa.Klask@eurekainc.com

Contact: Pei Wang, PhD; 510-654-7045; Pei.Wang@eurekainc.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

Contact: Claudia Aceves 626-218-5114 caceves@coh.org

Principal Investigator: Daneng Li, MD

United States, Kansas

Kansas University Medical Center; Recruiting

Westwood, Kansas, United States, 66205

Contact: Anna Davis 913-588-0242 adavis43@kumc.edu

Principal Investigator: Raed Al-Rajabi, MD

United States, New York

Roswell Park Comprehensive Cancer Center; Recruiting

Buffalo, New York, United States, 14263

Contact: Celia DeJong, PhD 716-845-8197 Celia.DeJohn@RoswellPark.org

Principal Investigator: Renuka Iyer, MD

Sponsors and Collaborators

Eureka Therapeutics Inc.

Investigators

• Study Director: Pei Wang, PhD; Eureka Therapeutics Inc.

More Information

• Responsible Party: Eureka Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT04864054
• Other Study ID Numbers: ETUS20GPC3AR124
• First Posted: April 28, 2021
• Last Update Posted: May 6, 2024
• Last Verified: May 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eureka Therapeutics Inc.:

Hepatocellular Carcinoma; Advanced HCC; Late-Stage HCC; Liver Cancer; Liver Neoplasm; Metastatic Liver Cancer; Metastatic HCC; T-cell therapy; Immunotherapy; HCC

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases