In 2021, Agios presented a comprehensive analysis of final data from the global Phase 3 ClarIDHy trial of the targeted anticancer drug ivosidenib (TIBSOVO) in patients with isocitrate dehydrogenase-1 (IDH1)-mutated cholangiocarcinoma at the American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCOGI), including mature overall survival (OS) results.
This study was conducted in patients with previously treated IDH1-mutated cholangiocarcinoma. The final analysis showed that patients in the ivosidenib treatment group had an improvement in the secondary endpoint of OS compared to the placebo group, but this was not statistically significant. Specifically, the median OS was 10.3 months in the ivosidenib treatment group and 7.5 months in the placebo group (HR=0.79; 95% CI: 0.56–1.12; one-sided p=0.093).
Notably, the clinical protocol stipulated that patients receiving placebo could switch to ivosidenib (TIBSOVO) if their disease progressed. In fact, a high proportion of patients in the placebo group (70.5%) switched to ivosidenib. Pre-specified cross-adjusted analysis using the rank-preserving structure failure time (RPSFT) model showed a median overall survival (OS) of 5.1 months in the placebo group (HR=0.49, 95% CI 0.34–0.70, one-sided p<0.0001). The safety observed in the study was consistent with previously published data.
IDH1 is a metabolic enzyme, and mutations in its gene are present in various tumors, including acute myeloid leukemia (AML), cholangiocarcinoma, and glioma. ivosidenib is a first-in-class, selective, and potent oral targeted inhibitor of IDH1-mutated cancers.
In terms of regulatory approval, ivosidenib (TIBSOVO) was approved by the U.S. FDA in July 2018 for adult patients with relapsed or refractory acute myeloid leukemia (R/RAML) confirmed by a diagnostic method (Abbott RealTime IDH1 companion diagnostic kit). This approval makes ivosidenib the first drug approved by the FDA for the treatment of IDH1-mutant R/RAML.
