The Food and Drug Administration (FDA) announced the approval of ivosidenib (Tibsovo) for advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation. 

Cholangiocarcinoma is a rare cancer that forms in the bile duct. Patients with cholangiocarcinoma are often diagnosed at a later stage when the prognosis is poor. The disease can be classified based on whether the cancer is in the bile duct within the liver (intrahepatic cholangiocarcinoma [iCCA]) or outside the liver (extrahepatic cholangiocarcinoma). Approximately 13% of patients with intrahepatic cholangiocarcinoma have IDH1 mutations.

The approval of ivosidenib for this indication was based on positive results from a randomized (2:1), multicenter, double-blind, placebo-controlled clinical trial (NCT02989857) of 185 adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation. The patient’s disease must have progressed following at least one, but not more than two prior regimens, including at least one gemcitabine- or 5-flurouracil-containing regimen. Patients were randomized to receive either ivosidenib 500 mg orally once daily or matched placebo until disease progression or unacceptable toxicity.

The primary efficacy endpoint of the study was progression-free survival (PFS) as determined by an independent review committee. The trial demonstrated a statistically significant improvement in PFS for patients randomized to ivosidenib. The analysis of OS was not significant as 70% of patients randomized to placebo had crossed over to receive ivosidenib after radiographic disease progression.

The most common adverse reactions (≥15%) in patients with cholangiocarcinoma were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.

Ivosidenib is also approved for the treatment of newly-diagnosed elderly patients with acute myeloid leukemia (AML) and a susceptible IDH1 mutation as well as adult patients with relapsed or refractory AML with a susceptible IDH1 mutation.

To stay up to date with the latest news in rare diseases, sign up for our weekly newsletter.