Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)

Summary

Study AG120-C-005 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of orally administered AG-120. Participants, all personnel involved in the evaluation of participants' response to treatment (e.g., Investigators, study coordinators, study pharmacists), and designated Sponsor team members will be blinded to study treatment. Participants are required to have a histologically-confirmed diagnosis of isocitrate dehydrogenase-1 (IDH1) gene-mutated cholangiocarcinoma that is not eligible for curative resection, transplantation, or ablative therapies prior to enrollment. IDH1 mutation testing will be performed at participating investigative sites. Participants must have progression of disease and have received at least 1 but not more than 2 prior treatment regimens for advanced disease (nonresectable or metastatic). All participants must have received either a gemcitabine or a 5 fluorouracil (5-FU) based chemotherapy regimen.

Timeline

Start

2017-02-20

Primary completion

2019-01-31

Completion

2021-05-17

Publications

• Background Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DV, Borad MJ, Bridgewater J, Harris WP, Murphy AG, Oh DY, Whisenant J, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Fan B, Wu B, Chamberlain CX, Jiang L, Gliser C, Pandya SS, Valle JW, Zhu AX. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807. doi: 10.1016/S1470-2045(20)30157-1. Epub 2020 May 13.
• Valle JW, Abou-Alfa GK, Kelley RK, Lowery MA, Shroff RT, Bian Y, Saint-Hilary G, Liu H, Teng Z, Hua Z, Gliser C, Vogel A, Javle MM. Quantitative benefit-risk assessment of data from the phase III ClarIDHy study of ivosidenib versus placebo in patients with mIDH1 cholangiocarcinoma. ESMO Gastrointest Oncol. 2025 Apr 3;8:100159. doi: 10.1016/j.esmogo.2025.100159. eCollection 2025 Jun.
• Fan B, Abou-Alfa GK, Zhu AX, Pandya SS, Jia H, Yin F, Gliser C, Hua Z, Hossain M, Yang H. Pharmacokinetics/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study. Cancer Chemother Pharmacol. 2024 May;93(5):471-479. doi: 10.1007/s00280-023-04633-5. Epub 2024 Jan 27.
• Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, Cleary JM, Catenacci DVT, Borad MJ, Bridgewater JA, Harris WP, Murphy AG, Oh DY, Whisenant JR, Lowery MA, Goyal L, Shroff RT, El-Khoueiry AB, Chamberlain CX, Aguado-Fraile E, Choe S, Wu B, Liu H, Gliser C, Pandya SS, Valle JW, Abou-Alfa GK. Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation: The Phase 3 Randomized Clinical ClarIDHy Trial. JAMA Oncol. 2021 Nov 1;7(11):1669-1677. doi: 10.1001/jamaoncol.2021.3836.

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Indications