Vactosertib (TEW-7197) is an investigational agent that inhibits the Transforming Growth Factor beta (TGFβ) signaling pathway. Myeloproliferative Neoplasms (MPN) are blood cancers known to have abnormal TGFβ signaling. Animal models of MPNs have shown that abnormal TGFβ signaling is primarily responsible for bone marrow fibrosis (scarring of the bone marrow). The bone marrow is the primary site for blood cell production, and when fibrosis occurs, this disturbs and alters the production of blood cells. Bone marrow fibrosis is also linked to the development of new sites of blood cell production outside of the bone marrow—called extramedullary hematopoiesis—in the spleen, liver and sometimes other sites.

Abnormal TGFβ signaling is thought to contribute to many of the problems experienced by patients with MPNs, including abnormal blood cell counts such as anemia. Anemia leads to symptoms such as fatigue and shortness of breath. By inhibiting TGFβ, vactosertib may block the abnormal functions of MPN cancer cells and improve anemia. It is hoped that by improving anemia, patients may feel better. We also hope that vactosertib may improve abnormal bone marrow fibrosis and help restore normal blood cell production in the bone marrow. 

Currently, the treatments of anemia in patients with MPNs include blood transfusions (receiving red blood cells intravensouly to replace the lack of functioning red blood cells), erythropoietin stimulating agents given as injections which will help stimulate red blood cell production in the bone marrow, and sometimes steroids. These interventions are supportive but are often insufficient and temporary as they are not capable of blocking the effects of the cancer cells causing anemia.

The purpose of this study is to assess how well vactosertib works in MPNs to improve anemia. This study will also provide new information about how vactosertib blocks TGFβ signaling in MPN cells and how this, in turn, can block MPN cancer cells themselves and/or their ill-effects on the bone marrow such as fibrosis. It is important for any drug to be safe. For this reason, the dose of vactosertib will be adjusted during the study to evaluate how well vactosertib works and to ensure that the dose used is not causing unexpected toxicities. The research team will monitor patients closely during the study.