FDA Grants Orphan Drug Designation to ET140203 T Cells for Hepatoblastoma


The FDA has given orphan drug designation to ET140203 ARTEMIS, an investigational therapy for hepatoblastoma, the safety and potential efficacy of which are being evaluated in the phase 1/2 ARYA-1 and ARYA-2 studies.

Novel T-cell therapy ET140203 (ARTEMIS) has been granted orphan drug designation by the FDA for the treatment of pediatric hepatoblastoma, according to a press release from Eureka Therapeutics, Inc.

The safety and efficacy of ET140203 is being investigated in 2 trials that are currently recruiting patients: the phase 1/2 ARYA-1 study (NCT04502082)—assessing the agent among adult patients—and the phase 1/2 ARYA-2 study (NCT04634357)—evaluating the agent in pediatric patients with hepatoblastoma, hepatocellular neoplasm not otherwise specified (NOS), and hepatocellular carcinoma.

“We are pleased to receive [orphan drug designation] for ET140203 following the FDA’s earlier grant of fast track designation and rare pediatric disease designation designations to ET140203 for the treatment of [hepatoblastoma],” Cheng Liu, MD, PhD, president and chief executive officer at Eureka Therapeutics, said in the press release. “These designations highlight the significant unmet medical need for better pediatric liver cancer treatment options.”

ET140203 is created using a patient’s collected T cells and are then engineered to express proprietary cell receptors before being infused back into patients. The therapy also expresses a T-cell receptor–mimic antibody that targets alpha fetoprotein (AFP) peptide/HLA-A2 complex in liver cancer cells.

The open-label phase 1/2 ARYA-2 study is designed to explore the safety and preliminary efficacy of ET140203 treatment among pediatric patients who are AFP- and HLA-A2–positive with relapsed/refractory disease. The study has an estimated enrollment of 25 participants. The first portion of the trial will assess the safety and tolerability of ET140203 in addition to determining the recommended phase 2 dose (RP2D) using a 3+3 dose escalation design. Primary outcome measures include the incidence of adverse effects (AEs) following ET140203 T-cell infusion, severity rates of AEs after infusion, incidence of dose limiting toxicities (DLTs) following infusion, and the RP2D based on DLTs. Secondary end points of the study include response rate and pharmacokinetics profile following infusion.

Patients with histologically confirmed hepatoblastoma, hepatocellular carcinoma, or hepatocellular neoplasm NOS between the ages of 1 to 21 years are eligible to participate in the study. Patients were also required to have a serum AFP of more than 200 ng/ml at the time of screening and after the most recent line of therapy. Additional inclusion criteria include disease reoccurrence after remission following initial standard-of-care treatment or lack of response to treatment, molecular human leukocyte antigen class I allele typing, and a life expectancy of more than 4 months. A Lanksy or Karnofsky performance status of 70 or higher and adequate organ function were also required.

Patients were excluded from the study if they received cytotoxic chemotherapy, radiation therapy, systemic corticosteroids, other anticancer therapies, or any other immunosuppressive agents within 2 weeks of leukapheresis and conditioning chemotherapy. Additional exclusion criteria include having active autoimmune disease requiring systemic immunosuppressive therapy; compromised circulation in the main portal vein, hepatic vein, or vena cava; a history of organ transplants; and hepatoblastoma, hepatocellular neoplasm NOS, or hepatocellular carcinoma involving more than 50% of the liver volumetrically.

In addition to ARYA-1 and ARYA-2, the ARYA-3 study (NCT04864054) is also currently enrolling participants to explore the safety and determine the RP2D of ECT204 T cells in adult patients with Glypican 3–positive hepatocellular carcinoma.


Eureka Therapeutics receives orphan drug designations for treatment of hepatoblastoma with ET140203 ARTEMIS® T cells. News release. Eureka Therapeutics, Inc. October 17, 2022. Accessed October 18, 2022. https://bwnews.pr/3yPHl18

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