ClarIDHy: focus on isocitrate dehydrogenase 1 (IDH1) mutations in your approach to advanced cholangiocarcinoma

The ClarIDHy Phase 3 clinical trial is actively recruiting patients with IDH1-mutated advanced cholangiocarcinoma. The trial will evaluate the safety and efficacy of AG-120, a targeted inhibitor of the IDH1 mutant protein.

Targeting IDH1 mutations

ClarIDHy is a multicenter, Phase 3, double-blind, placebo-controlled study of AG-120 for patients with advanced cholangiocarcinoma (nonresectable or metastatic) and an IDH1 mutation. 1 AG-120 is a first-in-class investigational agent that targets the mutated IDH1 enzyme.

The safety and efficacy of AG-120 have not been established. There is no guarantee that AG-120 will receive health authority approval or become commercially available for the use being investigated.

Among your patients with cholangiocarcinoma, 13-15% may have IDH1 mutations

Understanding the role of IDH1 mutations in cancer

Mutations in IDH1 may be present in 13%-15% of patients with cholangiocarcinoma. 2-4 Mutated IDH1 converts α-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), which accumulates in tumor cells. 2-HG modulates gene expression and alters DNA and histone methylation. 5,6

Diagram of mutated IDH1 converting α-KG in the cytosol to the oncometabolite 2-HG

Molecular profiling in cholangiocarcinoma

Molecular profiling can identify mutations associated with cancers, including mutations of IDH1. Tests for IDH1 mutations may be available as part of a gene panel or as gene-specific tests.

Testing for IDH1 mutations is provided by the ClarIDHy clinical trial at participating investigative sites. Molecular profiling will be done from a fresh tumor biopsy or the most recent banked tumor tissue available.

Molecular profiling identifies mutations. Diagrams of patient's DNA from normal cell and from cancerous cell

The ClarIDHy clinical trial is for patients with IDH1-mutated advanced cholangiocarcinoma

Key patient inclusion criteria 1

  • ≥18 years of age
  • Cholangiocarcinoma that is nonresectable or metastatic and not eligible for curative resection, transplantation, or ablative therapies
  • IDH1 gene-mutated disease based on testing provided by this clinical trial through a central laboratory
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least one evaluable and measurable lesion (RECIST v1.1)
  • Documented disease progression following at least 1, but no more than 2, prior treatment regimens in the advanced setting. Patients must have received at least 1 regimen containing gemcitabine or 5-fluorouracil (5-FU). Patients who have received systemic adjuvant chemotherapy are eligible provided there is documented disease progression during or within 6 months of completing the therapy

How to participate

To determine whether your patient may qualify to participate in the ClarIDHy clinical trial and to find clinical trial sites near you:

Contact Agios Medical Information

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Phone: 1.833.228.8474

Visit to locate a clinical trial site near you.


  1. Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy). U.S. National Institutes of Health. Accessed December 14, 2016.
  2. Borger DR, Tanabe KK, Fan KC, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist. 2012;17(1):72-79.
  3. Grassian AR, Pagliarini R, Chiang DY. Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol. 2014;30(3):295-302.
  4. Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Hum Pathol. 2012;43(10):1552-1558.
  5. McKenney AS, Levine RL. Isocitrate dehydrogenase mutations in leukemia. J Clin Invest. 2013;123(9):3672‌-3677.
  6. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010;18(6):553-567.