FDA Approves Ivosidenib for Advanced or Metastatic Cholangiocarcinoma

August 26, 2021

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On August 25, 2021, the Food and Drug Administration 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.

On August 25, 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 randomized (2:1), multicenter, double-blind, placebo-controlled clinical trial (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 randomized 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 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). The analysis of OS was not significant (0.79; 95% CI: 0.56, 1.12; p=0.093); 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 disease progression or unacceptable toxicity.

View full prescribing information for Tibsovo.

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. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 or by calling 1-800-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.

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Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.