IDH1-Mutant Advanced Cholangiocarcinoma (bile duct cancer) is a type of isocitrate dehydrogenase-1-mutated cancer that has spread beyond the bile ducts or had recurred after the treatment. Ivosidenib is a target inhibitor of mutant IDH1 and is under evaluation for the treatment of mIDH1 solid tumors. The objective of this study is to examine the safety and efficacy of ivosidenib in patients with mIDH1-cholangiocarcinoma.

This phase-1 dose-escalation and expansion study included a total of 73 patients with mIDH1-cholangiocarcinoma. The patients were assigned to dose escalation of ivosidenib, administered orally at 200–1,200 mg daily in 28-day cycles. The primary outcomes of the study were safety, tolerability, and the maximum tolerated dose of ivosidenib.

 No dose-limiting toxicities were reported during the study. The maximum tolerated dose was not reached, and 500 mg daily was selected for expansion. Common adverse effects that occurred in more than 20% of the patients were fatigue, diarrhea, nausea, abdominal pain, decreased appetite, and vomiting. Two patients (3%) suffered treatment-related adverse events leading to death. Median progression-free survival was 3.8 months, with the rates of 6-month and 12-month progression-free survival being 40.1% and 21.8%, respectively.

 The research concluded that ivosidenib at a high dose was efficacious and well-tolerated in patients with mIDH1-cholangiocarcinoma.