The therapy is currently being evaluated in the phase 1/2 ARYA-1, ARYA-2, and ARYA-3 studies in adults and children.
The FDA has granted orphan drug designation (ODD) to Eureka Therapeutics’ T-cell therapy ET140203 for the potential treatment of hepatoblastoma.1
"We are pleased to receive ODD for ET140203 following the FDA’s earlier grant of Fast Track Designation (FTD) and Rare Pediatric Disease Designation (RPDD) designations to ET140203 for the treatment of hepatoblastoma," Cheng Liu, PhD, founder, president and chief executive officer, Eureka Therapeutics, said in a statement.1 "These designations highlight the significant unmet medical need for better pediatric liver cancer treatment options."
ET140203 is developed using Eureka’s proprietary ARTEMIS cell receptor to express a T-cell receptor (TCR) mimic antibody that targets an alpha fetoprotein (AFP)-peptide/HLA-A2 complex on liver cancer cells. It also uses Eureka’s proprietary tumor infiltration technology that has demonstrated enhanced ability to infiltrate solid tumors in animal models.
ET140203 is currently being evaluated in the phase 1/2 ARYA-1 (NCT04502082), ARYA-2 (NCT04634357), and ARYA-3 (NCT04864054) studies. ARYA-1 isevaluating ET140203 ARTEMIS T cells directed with a TCR mimic antibody in adults with advanced hepatocellular carcinoma (HCC), ARYA-2 is evaluating the same formulation in children with hepatoblastoma, hepatocellular malignant neoplasm, not otherwise specified or HCC, and ARYA-3 study is evaluating ECT204 T cells targeting the glypican 3 (GPC3) protein expressed on the surface of liver cancer cells in adults with advanced HCC.
The ARYA-2 study was initiated in early 2022 and is open for enrollment at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.2 It is enrolling patients between the ages of 1 and 21 years with relapsed, histologically confirmed HLA-A2+ hepatoblastoma, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of screening.Participants must have a life expectancy of over 4 months, a score of over 70 on Lansky or Karnofsky Performance Scales, a Child-Pugh score of B7 or better, adequate organ function, and at least 1 lesion at least 5 mm in diameter or 2 or more lesions at least 3 mm in diameter. For the dose-expansion cohort, subjects must have measurable disease by RECIST v1.1.
At months 1, 3, 6, 9, 12, 18, and 24 after treatment, investigators will measure tumor response assessments, imaging and serum AFP levels. Participants will be followed for 15 years post-treatment for further safety and overall survival assessments. The study is primarily evaluating incidence and severity of adverse events (AEs) and dose-limiting toxicities. Secondary outcome measures include efficacy and pharmacokinetics.
“Relapsed or refractory pediatric liver cancers are rare, have limited treatment options, and remain difficult to treat,” principal investigator Allison F. O'Neill, MD, clinical director, Solid Tumor Program, and director, Medical Therapies, Liver Tumor Center of Excellence, Dana-Farber/Boston Children’s, said in a previous statement.2 “Engineered T-cell therapies have the potential to transform the outcome of patients with difficult-to-treat liver cancers. We are thrilled to work with Eureka Therapeutics and initiate a trial of ET140203 T-cell therapy for pediatric and adolescent patients with relapsed or refractory liver tumors.”