A Phase 1/1b clinical trial has begun in Australia to evaluate an investigational CAR-T cell therapy for patients with EPHB4-positive solid tumours, marking another step forward in the development of cell therapies for cancers that have traditionally proved difficult to treat.

The multicentre CartiEr E312 study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of ACS2015, an autologous CAR-T therapy developed by A-SEEDS. The trial plans to enrol up to 48 patients with colorectal cancer, hepatocellular carcinoma, and bone and soft tissue sarcomas.

Unlike approved CAR-T therapies, which have largely focused on blood cancers, ACS2015 is designed to target EPHB4, a protein that is overexpressed in several solid tumour types and is being investigated as a potential therapeutic target.

The therapy also incorporates a manufacturing approach that allows production from cryopreserved patient-derived blood cells, providing greater flexibility in patient collection and manufacturing scheduling during clinical development.

Cell Therapies will manufacture ACS2015 for patients enrolled in the Australian study. The company will be responsible for the GMP production of the investigational therapy throughout the trial.

Solid tumours remain one of the most challenging areas for CAR-T cell therapy development. While the treatment approach has transformed outcomes for some patients with haematological malignancies, achieving similar success in solid cancers has been limited by factors including tumour heterogeneity, immune suppression within the tumour microenvironment and difficulties in identifying suitable targets.

By focusing on EPHB4, researchers hope to evaluate whether the target can provide a new therapeutic approach across multiple solid tumour types.

The Phase 1/1b study is designed primarily to evaluate safety while also collecting early evidence of biological activity and anti-tumour effects. Data from the trial will help determine the future clinical development pathway for ACS2015.

The Australian study forms part of A-SEEDS’ broader CAR-T development programme. The company is also evaluating AP8901, another EPHB4-targeted CAR-T therapy, in the Phase 1 CartiEr E211 study for patients with Ewing sarcoma and other solid tumours in Japan.

In addition, A-SEEDS is developing AS116, a CAR-T therapy targeting the granulocyte-macrophage colony-stimulating factor receptor (GMR), which is being evaluated in the Phase 1/2 CartiEr G111 study for patients with acute myeloid leukaemia.

As interest continues to grow in extending CAR-T therapies beyond blood cancers, the CartiEr E312 trial will contribute further clinical data on the feasibility of targeting EPHB4-positive solid tumours using autologous cell therapy.