Trial Initiated for Pediatric Liver Cancer Cell Therapy

The phase 1/2 ARYA-2 trial will be run in parallel with the similar phase 1/2 ARYA-1 and ARYA-3 trials.

Eureka Therapeutics has initiated the phase 1/2 ARYA-2 trial (NCT04634357) of the ET140203 ARTEMIS T-cell therapy in pediatric patients with relapsed or refractory hepatoblastoma (HB), hepatocellular neoplasm not otherwise specified (HCN-NOS), or hepatocellular carcinoma (HCC).1

“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 statement.1 “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.”

The phase 1 portion of the open-label, dose escalation, multi-center ARYA-2 trial is now open for enrollment at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. The ARYA-2 trial is being run in parallel with the phase 1/2 ARYA-1 (NCT04502082) trial that commenced in October 2020 and the phase 1/2 ARYA-3 (NCT04864054) trial that commenced in July 2021, both of which are evaluating T-cell therapies in adult patients with HCC. The ARYA-1 and ARYA-2 trials are evaluating ET140203 targeted toward the AFP-peptide/HLA-A2 complex while ARYA-3 is evaluating the ECT204 T-cell therapy targeted toward the GPC3 protein.

Eureka’s cell therapies are developed using their ARTEMIS platform, whichuses proprietary tumor infiltration technology designed to enhance the ability of cell therapies to infiltrate solid tumors. The approach has shown efficacy in animal models. The FDA previously granted ET140203 fast track designation for the treatment of HB and HCC in pediatric patients as well as rare pediatric disease designation for the treatment of HB.

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“Eureka recognizes the highly unmet medical need in treating pediatric patients with advanced liver cancers,” Cheng Liu, PhD, founder, president, and chief executive officer, Eureka Therapeutics, added to the statement.1 “We are pleased to be working with Dana-Farber to address it by bringing ARTEMIS® T-cell therapies to patients in the clinics.”

Eureka Therapeutics has other ventures in treating solid tumors; in November 2021, the company announced a collaboration with Imugene2 which will evaluateImugene’s CD19 onCARlytics oncolytic virus technology in combination with Eureka's anti-CD19 T-cell therapies. The approach previously demonstrated efficacy in preclinical studies in mouse models conducted by the City of Hope Comprehensive Cancer Center.

“We are delighted to be working with Imugene on tackling solid tumours using this innovative approach,” Liu said in a previous statement.2 “We believe our ARTEMIS® T-cell platform to be the ideal one to evaluate this combination. In head-to-head pre-clinical studies against CAR-T cells, our ARTEMIS® T-cells demonstrated superior efficacy, enhanced tumour infiltration, and less T-cell exhaustion. In the clinical context, our ARTEMIS® T-cells have demonstrated reduced cytokine release syndrome and other cytokine-related toxicities compared to CAR-T cells, potentially improving the efficacy and safety of a combination approach.”

REFERENCES
1. Eureka Therapeutics announces initiation of phase I/II ARYA-2 clinical trial of ET140203 ARTEMIS® T cells to treat pediatric liver cancer. News release. New release. Eureka Therapeutics. November 18, 2021. https://pipelinereview.com/index.php/2021111879731/DNA-RNA-and-Cells/Eureka-Therapeutics-Announces-Initiation-of-Phase-I/II-ARYA-2-Clinical-Trial-of-ET140203-ARTEMIS-T-Cells-to-Treat-Pediatric-Liver-Cancer.html
2. Imugene and Eureka Therapeutics announce strategic collaboration to accelerate advancement of oncolytic virus and T-cell therapy in solid tumours. News release. Eureka Therapeutics. November 1, 2021. https://www.eurekatherapeutics.com/media/press-releases/110121/