Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation

The study was done to test a cancer drug called ivosidenib (also called AG-120 or TIBSOVO) in participants with advanced solid tumors, including chondrosarcoma, cholangiocarcinoma and glioma.

Solid tumor cancers are abnormal growths of cells in organ(s) of the body such as the lung, breast, or brain. In advanced stages of the disease, solid tumors may spread in other parts of the body.

Glioma is a type of brain cancer that begins in ‘glial’ cells (the cells that surround and support nerve cells). It is a serious and rare disease with few effective treatment options. Chondrosarcoma is a rare type of cancer that starts in the bones. Cholangiocarcinoma is a cancer of the bile ducts. Bile ducts are tiny tubes carrying bile (a fluid produced in the liver that helps to break down fats during digestion) from liver to the intestine.

In several types of cancer such as gliomas, chondrosarcoma and cholangiocarcinoma, an abnormal form of a protein called Isocitrate dehydrogenase 1 (IDH1) is present in the tumor cells due to changes called mutations. When IDH1 is present in mutated form, it produces an excess amount of 2-hydroxyglutarate (2-HG), which is a substance that is normally present in cells in low levels. When 2-HG is present in excessive amounts, it impairs normal cell functioning and may cause them to become tumor cells.

Ivosidenib is a drug that blocks the activity of abnormal IDH1 proteins and may reduce 2-HG levels in tumor cells back to normal levels. Ivosidenib has already been approved in many countries to treat people who have cholangiocarcinoma and acute myeloid leukaemia, a type of cancer in the blood and bone marrow (the spongy tissue inside bones where blood cells are made).

The main objectives of the study were:

• To look at the safety of ivosidenib.
• To find the highest dose of ivosidenib that participants could take without too much risk (highest tolerated dose). This highest tolerated dose helps to find the recommended dose (the one that is both safe and effective for patients).