Zhu AX, Macarulla T, Javle MM, et al. - Treatment with ivosidenib (AG-120)—a first-in-class, oral, small-molecule inhibitor of mutant IDH1 (isocitrate dehydrogenase 1)—conferred clinical benefit in advanced cholangiocarcinoma with IDH1 mutation, compared with placebo, as evident based on the combined efficacy data and tolerable safety profile, as well as corroborating quality of life data.

• IDH1 variations occur in up to roughly 20% of patients with intrahepatic cholangiocarcinoma, and significantly improved progression-free survival with ivosidenib vs placebo was obtained in the ClarIDHy trial.

• This multicenter, randomized, double-blind, placebo-controlled, clinical phase 3 trial included 187 previously treated patients with advanced cholangiocarcinoma with IDH1 mutation.

• They were randomized to receive ivosidenib (n = 126) or placebo (n = 61); 43 patients crossed over from placebo to ivosidenib.

• Ivosidenib conferred numerically improved overall survival benefits vs placebo, despite a high rate of crossover; median overall survival was 10.3 months with ivosidenib vs 7.5 months with placebo (hazard ratio, 0.79).

• Ivosidenib preserved certain quality of life subscales and demonstrated good tolerability.