On 25 August 2021, the US Food and Drug Administration (FDA) approved ivosidenib (Tibsovo, Servier Pharmaceuticals LLC) 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.

The FDA also approved the Oncomine Dx Target Test (Life Technologies Corporation) as a companion diagnostic device to aid in selecting patients with cholangiocarcinoma for treatment with ivosidenib.

Ivosidenib was investigated in a randomised (2:1), multicentre, double-blind, placebo-controlled clinical study (Study AG120-C-005, 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 randomised to receive either ivosidenib 500 mg orally once daily or matched placebo until disease progression or unacceptable toxicity.

The primary efficacy endpoint was progression-free survival (PFS) as determined by independent review committee according to RECIST v1.1.

The study demonstrated a statistically significant improvement in PFS for patients randomised to ivosidenib (hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.25, 0.54; p < 0.0001).

The analysis of overall survival was not significant (HR 0.79; 95% CI 0.56, 1.12; p = 0.093); 70% of patients randomised 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, diarrhoea, cough, decreased appetite, ascites, vomiting, anaemia, and rash.

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

Full prescribing information for Tibsovo is available here.

This review used the Assessment Aid from the applicant to facilitate the FDA’s assessment.

This application was granted priority review, fast track designation, and orphan product designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.