T-Cell Therapy for Advanced Liver Cancer

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)

This study is testing a new T-cell therapy to see if it can help adults with advanced liver cancer that has a specific marker called GPC3.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Eureka Therapeutics Inc. (industry)
• Drugs / interventions: radiation
• Locations: 7 sites (Duarte, California and 6 other locations)
• Trial ID: NCT04864054 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of an investigational T-cell therapy, ECT204, in adults with advanced hepatocellular carcinoma (HCC) that expresses GPC3. The study involves collecting and genetically modifying patients' T cells to target and destroy cancer cells expressing GPC3. It consists of a Phase I component that has concluded and a Phase II expansion phase with two arms: one receiving ECT204 alone and the other receiving regorafenib prior to ECT204. Participants will be monitored for safety and overall survival over a period of up to 15 years.

Who should consider this trial

Good fit: Ideal candidates are adults with GPC3-positive advanced HCC who have failed or not tolerated at least two different systemic therapies.

Not a fit: Patients with pre-existing conditions that limit compliance or those without GPC3-positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced liver cancer who have limited alternatives.

How similar studies have performed: Other studies have shown promise with T-cell therapies targeting specific cancer markers, suggesting potential for success in this approach.

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 v1.1.
* 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.

Where this trial is running

Duarte, California and 6 other locations

• City of Hope — Duarte, California, United States (RECRUITING)
• Kansas University Medical Center, Principal Investigator: — Westwood, Kansas, United States (COMPLETED)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (RECRUITING)
• Oregon Health and Sciences University — Portland, Oregon, United States (RECRUITING)
• University of Texas Southwestern, Harold C. Simmons Comprehensive Cancer Center — Dallas, Texas, United States (RECRUITING)
• Fred Hutchinson Cancer Center, University of Washington — Seattle, Washington, United States (RECRUITING)
• National Taiwan University Cancer Center — Taipei, Taiwan (RECRUITING)

Study contacts

• Study coordinator: Teresa Klask, MBA

Conditions: Hepatocellular Carcinoma, Liver Cancer, Adult, Liver Neoplasm, Metastatic Liver Cancer, Advanced HCC, Late-Stage HCC, Liver Cancer, Metastatic HCC