The Food and Drug Administration (FDA) has approved Tibsovo® (ivosidenib) for the treatment of 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 approval was based on data from the double-blind, placebo-controlled ClarIDHy study (ClinicalTrials.gov Identifier: NCT02989857), which included 185 adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation whose disease had progressed following at least 1 but not more than 2 prior regimens, including at least 1 gemcitabine- or 5-FU-containing regimen.
Patients were randomly assigned to receive ivosidenib 500mg orally once daily or placebo until disease progression or unacceptable toxicity. The primary efficacy endpoint was progression free survival (PFS).
Findings showed that treatment with ivosidenib led to a statistically significant improvement in PFS (hazard ratio [HR] 0.37; 95% CI [0.25-0.54], P <.0001). Median PFS was 2.7 months (95% CI, 1.6-4.2) in the ivosidenib arm and 1.4 months (95% CI, 1.4-1.6) in the placebo arm.
Approximately 70% of patients in the placebo arm crossed over to ivosidenib at the time of disease progression. Though not statistically significant, a numeric improvement in overall survival (OS; secondary endpoint) was observed with ivosidenib vs placebo. Median OS was 10.3 months (95% CI, 7.8-12.4) for ivosidenib and 7.5 months (95% CI, 4.8-11.1) for placebo without adjusting for crossover.
The most common adverse reactions reported were fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash.
The FDA also approved Thermo Fisher Scientific’s Oncomine Dx Target Test as a companion diagnostic to identify patients with IDH1 mutated cholangiocarcinoma who may be candidates for Tibsovo. Patients should be selected for treatment based on the presence of IDH1 mutations.
Tibsovo is supplied as 250mg tablets.
- Servier announces FDA approval of Tibsovo® (ivosidenib tablets) in IDH1-mutated cholangiocarcinoma. News release. August 25, 2021. https://www.prnewswire.com/news-releases/servier-announces-fda-approval-of-tibsovo-ivosidenib-tablets-in-idh1-mutated-cholangiocarcinoma-301363055.html.
- FDA approves NGS-Based companion diagnostic for previously treated IDH1-mutated cholangiocarcinoma. News release. August 25, 2021. https://www.prnewswire.com/news-releases/fda-approves-ngs-based-companion-diagnostic-for-previously-treated-idh1-mutated-cholangiocarcinoma-301363031.html.
- Tibsovo [package insert]. Boston, MA: Servier Pharmaceuticals LLC. 2021.