Novel Non-Viral CAR-T Therapy AP8901 Enters Phase I Trial for EPHB4-Positive Solid Tumors
Key Insights
A Phase I clinical trial is evaluating AP8901, a novel non-viral CAR-T cell therapy (search) targeting EPHB4 (search) receptor-expressing solid tumors (search) including Ewing sarcoma (search).
The therapy uses innovative piggyBac transposon and genetically modified feeder cell methods to enable stable CAR protein expression while preventing T cell exhaustion.
AP8901 demonstrated therapeutic efficacy and tolerability in preclinical studies using rhabdomyosarcoma (search) mouse models.
The National Cancer Center Hospital East in Japan has initiated a Phase I clinical trial for AP8901, a groundbreaking non-viral CAR-T cell therapy (search) designed to target solid tumors (search) expressing the EPHB4 (search) receptor. This innovative treatment approach represents a significant advancement in cellular immunotherapy for patients with limited treatment options.
Novel Targeting Mechanism
AP8901 CAR-T cell therapy (search) specifically recognizes and eliminates EPHB4 (search) receptor-expressing malignant tumor cells by modifying the natural EPHB4 receptor ligand, ephrin B2 (search). The Ephrin type-B receptor 4 (EPHB4) is overexpressed on the surface of various tumor cells, including cells from malignant bone and soft-tissue tumors (search), making it an attractive therapeutic target.
Advanced Manufacturing Technology
The therapy distinguishes itself through its non-viral gene modification approach, utilizing piggyBac transposon and genetically modified feeder cell methods. This innovative manufacturing process enables stable expression of CAR proteins in T cells while preventing T cell exhaustion, a common limitation in traditional CAR-T therapies. The preclinical validation demonstrated therapeutic efficacy and tolerability in mice transplanted with rhabdomyosarcoma (search) cells.
Clinical Trial Design
The ongoing study is structured as a single-center, single-arm, dose-escalation Phase I trial evaluating the safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary anti-tumor activity of a single intravenous dose of AP8901. The trial targets patients with Ewing sarcoma (search) or solid tumors (search) expressing the EPHB4 (search) receptor.
Patient Selection Criteria
Key inclusion criteria require subjects with histologically diagnosed Ewing sarcoma (search) or solid tumor with confirmed metastasis or recurrence, or those with no standard treatment options for metastasis or recurrence, or patients refractory or intolerant to standard treatment. Eligible patients must have measurable or evaluable disease according to RECIST version 1.1 criteria and recent biopsy or surgical resection specimens showing prescreening immunohistochemistry positive for EPHB4 (search) in ≥1% of tumor cells.
Additional requirements include ECOG performance status 0 or 1 and subjects expected to survive ≥3 months from enrollment date. The study is being conducted at the National Cancer Center Hospital East, representing a collaborative effort between multiple departments including Experimental Therapeutics, Medical Oncology, Hematology, and the Division of Cancer Immunotherapy.