Ivosidenib, Nivolumab, and Ipilimumab Combination in Previously Treated Subjects With Nonresectable or Metastatic IDH1 Mutant Cholangiocarcinoma

This study was done to test a cancer drug called ivosidenib (also called S095031 or AG-120) in combination with nivolumab and ipilimumab. The study involved participants with a type of advanced bile duct cancer called cholangiocarcinoma whose cancer cells had a change (mutation) in the isocitrate dehydrogenase 1 (IDH1) gene.
In several types of cancer such as cholangiocarcinoma, an abnormal form of a protein IDH1 is present in the tumor cells due to changes called mutations. When IDH1 is mutated, it produces too much 2‑hydroxyglutarate (2-HG), which is a substance that is normally present in cells in low levels. Too much 2-HG can change how normal cells function and may cause them to become tumor cells.
Ivosidenib is a drug that blocks the activity of abnormal IDH1 proteins and reduces 2-HG levels in tumor cells to normal levels. Ivosidenib is already available to treat cholangiocarcinoma and certain blood cancers in some countries.

In this study, ivosidenib was combined with nivolumab and ipilimumab. These 2 medicines are immune check point inhibitors that help the immune system kill cancer cells. They are available in some countries to treat various types of tumors. Researchers hoped that using ivosidenib with nivolumab and ipilimumab will work better than using ivosidenib alone.
The study had 2 parts. The main objectives of this study were:

• Part 1: to assess the safety of ivosidenib in combination with nivolumab and ipilimumab and to find the recommended dose of ivosidenib (the one that is both safe and effective for patients) when given in combination with nivolumab and ipilimumab.
• Part 2: to see how well ivosidenib works in combination with nivolumab and ipilimumab.