GPC3-Targeted T-Cell Therapy (ECT204) in Adults With Advanced HCC

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 experienceddisease 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 limitcompliance with study requirements.

• Active, uncontrolled systemic bacterial, fungal, or viral infection. Subjects withHuman Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C are eligibleprovided their infection is being treated and the viral load is controlled.

• History of malignancy other than HCC within 5 years before screening, exceptadequately 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 beenadequately treated (no evident neurological deficit and no steroid or anti-epileptictherapy for brain metastases) are eligible.

• Pregnant or lactating women.

• Currently receiving or ending (< 14 days from date of consent) liver tumor-directedtherapy (e.g., radiation, ablation, embolization), or hepatic surgery.

• Concurrently receiving other investigational agents, biological, chemical, orradiation 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 anyinvasion into the inferior vena cava (IVC), except for subjects with IVC invasionwho have been treated and radiographically stable for at least 6 months prior toscreening.

• Ascites requiring active treatment, such as a requirement for paracentesis orescalation of diuretic doses. Exception: Subjects maintained on a stable dose ofdiuretics 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 monthsprior to screening.

• Coagulation abnormality defined as international normalized ratio (INR) > 1.7,unless the elevation is due to therapeutic anticoagulation that, in theInvestigator'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), mouseimmunoglobulin, 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 conditioningagents