Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation (PyramIDH)

This study is needed to test a drug called ivosidenib in adults with myelodysplastic syndrome (MDS) that has never been treated with a class of drugs called hypomethylating agents (HMA) and that carries a specific gene change, called an isocitrate dehydrogenase-1 (IDH1) mutation. MDS is a group of disorders in which the bone marrow (the spongy tissue inside the bones) does not make enough healthy blood cells or platelets. MDS leads to low blood cell count, which can increase the risk of infection and progression to Acute Myeloid Leukemia (AML). AML is an aggressive form of white blood cell cancer.

In several types of cancer, an abnormal form of a protein called isocitrate dehydrogenase 1 (IDH1) is present in the cancer cells due to gene changes called mutations. When IDH1 is present in its abnormal form, it produces too much 2-hydroxyglutarate (2HG). This impairs normal cell functioning and may cause cells to become cancer cells. Ivosidenib is a drug that blocks the activity of abnormal IDH1 proteins and thus may reduce 2-HG levels in cancer cells to normal levels.

In this study, participants receive either ivosidenib or azacitidine. Azacitidine is an HMA, a standard treatment for MDS.

The main goal of this study is to see if ivosidenib is an effective treatment for participants with MDS and an IDH1 mutation.