Rebastinib is an orally administered, potent and selective inhibitor of the TIE2 immunokinase. TIE2 is the receptor for angiopoietins, an important family of vascular growth factors, and has an important role in regulating tumor angiogenesis, invasiveness, metastasis, and immunotolerance. TIE2 is expressed in protumoral M2 macrophages known as “TIE2 expressing macrophages”, or TEMs. Rebastinib is in clinical development for the treatment of multiple solid tumors and in combination with chemotherapy in an investigator sponsored Phase 1b trial.
|Tumor Type||Target||Status||Retained Rights|
Combo with Chemo
|TIE2 inhibitor||Phase 1 Trial – Ongoing||Worldwide|
Rationale for Rebastinib in Solid Tumors:
The activity of rebastinib was evaluated in a model in which breast cancer growth and metastases can be assessed. In this model, tumor growth leads to metastasis, which is known to be modulated by TEMs, including a subset of TEMs which form structures in blood vessels that aid the metastatic spread of the cancer. The activity of rebastinib was evaluated on its own and in combination with paclitaxel, an inhibitor of microtubule dynamics. In this preclinical disease model, treatment with rebastinib significantly decreased tumor growth, reduced blood microvessel density, inhibited the TEMs, and significantly reduced the number of circulating tumor cells and metastases.
Based on these findings, Deciphera plans to explore the clinical development of rebastinib in multiple solid tumors in combination with chemotherapy or immuno-oncology agents.