Evidence map›Paper›PMID 38278871›Full record

Trial reportCancer chemotherapy and pharmacology2024

Pharmacokinetics/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study.

Bin Fan, Ghassan K Abou-Alfa, Andrew X Zhu, Shuchi S Pandya, Hongxia Jia, Feng Yin, Camelia Gliser, Zhaowei Hua, Mohammad Hossain, Hua Yang

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02989857 (A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation), which is not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.4field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02989857 phase3completednot on this map

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-controlled Study of AG-120 in Previously-treated Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

TypeinterventionalSponsorInstitut de Recherches Internationales ServierRan2017 to 2021Enrolled187ConditionsAdvanced Cholangiocarcinoma, Metastatic CholangiocarcinomaArmsAG-120, Placebo
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 6 citations in OpenAlex.

  1. Review
  2. Article
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  4. Article
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  7. Digestive cancers: mechanisms, therapeutics and management.Signal transduction and targeted therapy · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Bin FanAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Ghassan K Abou-AlfaMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Andrew X ZhuMassachusetts General Cancer Center, Harvard Medical School, Boston, MA, USA.
Shuchi S PandyaAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Hongxia JiaAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Feng YinAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Camelia GliserAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Zhaowei HuaServier Pharmaceuticals LLC, 200 Pier Four Boulevard, Boston, MA, 02210, USA.
Mohammad HossainAgios Pharmaceuticals Inc., Cambridge, MA, USA. mohammad.hossain@servier.com.ORCID 0000-0002-9147-7917
Hua YangAgios Pharmaceuticals Inc., Cambridge, MA, USA.
Agios Pharmaceuticals (United States) · USHarvard University · USMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

purposeReport pharmacokinetic (PK)/pharmacodynamic (PD) findings from the phase III ClarIDHy study and any association between PK/PD parameters and treatment outcomes in this population.

methodsPatients with mutant isocitrate dehydrogenase 1 (mIDH1) advanced cholangiocarcinoma were randomized at a 2:1 ratio to receive ivosidenib or matched placebo. Crossover from placebo to ivosidenib was permitted at radiographic disease progression. Blood samples for PK/PD analyses, a secondary endpoint, were collected pre-dose and up to 4 h post-dose on day (D) 1 of cycles (C) 1 - 2, pre-dose and 2 h post-dose on D15 of C1 - 2, and pre-dose on D1 from C3 onwards. Plasma ivosidenib and D-2-hydroxyglutarate (2-HG) were measured using liquid chromatography-tandem mass spectrometry. All clinical responses were centrally reviewed previously.

resultsPK/PD analysis was available for samples from 156 ivosidenib-treated patients. Ivosidenib was absorbed rapidly following single and multiple oral doses (time of maximum observed plasma concentration [T

conclusionOnce-daily ivosidenib 500 mg has a favorable PK/PD profile, attesting the 2-HG reduction mechanism of action and, thus, positive outcomes in treated patients with advanced mIDH1 cholangiocarcinoma. CLINICAL

trial registrationNCT02989857 Registered February 20, 2017.

Indexed as

Antineoplastic AgentsBile Duct NeoplasmsCholangiocarcinomaGlycineIsocitrate DehydrogenaseMutationPyridinesAdultAgedAged, 80 and overCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMiddle AgedAntineoplastic AgentsGlycineIDH1 protein, humanIsocitrate DehydrogenaseivosidenibPyridinesCholangiocarcinomaD-2-hydroxyglutarateIsocitrate dehydrogenaseIvosidenibPharmacodynamicsPharmacokinetics

Identifiers

PMID38278871
PMCPMC11043204
OpenAlexW4391269798

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.