On August 25, 2021, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo®) for adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. FDA also approved the Oncomine Dx Target Test as a companion diagnostic device to aid in selecting patients with cholangiocarcinoma for treatment with ivosidenib.

FDA Approves Ivosidenib for Advanced or Metastatic Cholangiocarcinoma

Ivosidenib was investigated in a randomized (2:1), multicenter, double-blind, placebo-controlled clinical trial (AG120-C-005; NCT02989857) of 185 adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation. Patients’ 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 they experienced disease progression or unacceptable toxicity.

The primary efficacy endpoint was progression-free survival (PFS) as determined by independent review committee according to response evaluation criteria in solid tumors 1.1. The trial demonstrated a statistically significant improvement in PFS for patients randomized to ivosidenib (HR = 0.37; 95% CI = 0.25, 0.54; p < 0.0001). Overall survival analysis was not significant (HR = 0.79; 95% CI = 0.56, 1.12; p = 0.093), and 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.

The recommended ivosidenib dosage for cholangiocarcinoma is 500 mg orally once daily with or without food until patients experience disease progression or unacceptable toxicity.

View the full prescribing information for ivosidenib.

The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.

FDA granted the application priority review, fast track designation, and orphan product designation. A description of FDA expedited programs is in the Guidance for IndustryꟷExpedited Programs for Serious ConditionsꟷDrugs and Biologics.

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.