Moving EphB4 Therapeutics to Pediatric Phase I/II Trials

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood with a propensity to metastasize early. Despite 40 years of cooperative group trials of intensified chemotherapy, the dismal survival for metastatic disease is unimproved. Targeted therapies are now needed.

The focus of this project is interaction of tumor cells with the tumor bed through the cell surface Eph receptor kinase called EphB4. We have preliminary preclinical evidence that EphB4 is among the very highest value targets of the family of growth factor receptors for rhabdomyosarcoma. In partnership with Vasgene Therapeutics, we will test two investigational agents in preclinical rhabdomyosarcoma models. The first agent is an anti-EphB4 antibody. The second agent is a nanoparticle(albumin)-bound soluble EphB4 receptor.

Our studies will be performed in close communication with the NCI CTEP Pediatric Preclinical Testing Program, of which Dr. Keller is a Consultant. If effectiveness of one or both agents is seen in mouse models, this antibody will investigated by the Children's Oncology Group Phase I Program.  Subsequently, Phase II studies in rhabdomyosarcoma can be pursued by the Children's Oncology Group Soft Tissue Sarcoma Committee.