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Cholangiocarcinoma News

IDH1 Mutation Detection in ctDNA and Association with Clinical Response in Patients with Advanced iCCA from Phase 3 ClarIDHy

Web Exclusives — May 30, 2020

Mutations in IDH1 are detected in approximately 13% of patients with intrahepatic cholangiocarcinoma (iCCA). ClarIDHy was a global, phase 3, double-blind study in previously treated patients with advanced mutated IDH1 iCCA.1 ClarIDHy tested ivosidenib, a first-in-class, oral inhibitor of the mutant IDH1 (mIDH1) protein versus placebo in previously treated patients. Ivosidenib demonstrated an improvement in progression-free survival (PFS) versus placebo (hazard ratio, 0.37; P <.001).2 Feasibility of mIDH1 detection in plasma circulating tumor cells (ctDNA) from patients with iCCA was demonstrated in this study and was highly concordant with mutation status in tumor tissue. This analysis was extended to the larger patient cohort from ClarIDHy, and longitudinal mIDH1 detection from ctDNA was assessed and correlated with clinical response.

Formalin-fixed, paraffin-embedded tissues were used to analyze for confirmation of mIDH1 detection. Pretreatment plasma samples from all patients were collected, and longitudinal samples from patients enrolled were obtained on day 1 of each treatment cycle. mIDH1 detection in plasma ctDNA and tissue was concordant in 92% (193/210) of samples screened. Longitudinal analysis with biomarker data available as of January 2020 demonstrated IDH1-MC in plasma from 10 ivosidenib-treated patients with PFS ≥2.7 months (n = 36) versus 0 patients with PFS <2.7 months (n = 55).

The authors concluded that the feasibility of mIDH1 detection in plasma ctDNA from patients with iCCA was demonstrated and was highly concordant with mutation status in tumor tissue. number NCT02989857.


  1. Aguado E, et al. ASCO 2020. Abstract 4576.
  2. Abou-Alfa G, et al. Ann Oncol. 2019;30(suppl_5):v851-v934.

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