# Ivosidenib

Source: https://onco.cc/drugs/ivosidenib/  
OnCo record `ivosidenib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.

## Summary

Approved 2018 (relapsed/refractory IDH1 AML), 2019 (newly diagnosed unfit, monotherapy), 2022 (with azacitidine, AGILE: EFS HR 0.33, OS 24.0 vs 7.9 months, HR 0.44), 2021 (IDH1 cholangiocarcinoma), and 2023 (IDH1 MDS). Servier acquired the Agios oncology portfolio in 2021. Differentiation syndrome is the class toxicity; isocitrate-dehydrogenase-2 isoform switching and second-site IDH1 mutations cause resistance.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Tibsovo
- Modality: Small-molecule IDH1 inhibitor
- Mechanism: Allosteric inhibitor of mutant IDH1; blocks 2-hydroxyglutarate production, restoring TET2-dependent demethylation and differentiation.
- Approvals: US 2018: Relapsed/refractory IDH1-mutated AML; US 2019: Newly diagnosed IDH1-mutated AML unfit for intensive chemotherapy; US 2021: Previously treated IDH1-mutated cholangiocarcinoma; US 2022: Newly diagnosed IDH1-mutated AML with azacitidine (AGILE); US 2023: Relapsed/refractory IDH1-mutated MDS; UK 2024: Locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation after one or more systemic treatments; NICE TA948 recommended 31 January 2024 with a commercial arrangement
- Dosing: Oral; 500 mg once daily with or without food (avoid high-fat meals), until progression; with azacitidine 75 mg/m² days 1-7 of 28
- Toxicity (grade 3+): Neutropenia 27%

## Notes

- In cholangiocarcinoma: ClarIDHy showed PFS of 2.7 versus 1.4 months (HR 0.37) and a crossover-adjusted OS benefit in previously treated IDH1-mutant disease, approved in August 2021; the response rate was 2 percent, so disease stabilisation is the benefit. In ClarIDHy nausea affected 41 percent, diarrhoea 35 percent, fatigue 31 percent and grade 3 or higher ascites 9 percent.
- Gallbladder cancer: 91 percent of ClarIDHy patients had intrahepatic cholangiocarcinoma (Tibsovo label), and IDH1 mutations are an intrahepatic feature, so ivosidenib has minimal evidence in gallbladder cancer; the licence wording is cholangiocarcinoma.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ivosidenib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Ivosidenib
- NICE TA948: ivosidenib for IDH1 R132 cholangiocarcinoma (31 January 2024): https://www.nice.org.uk/guidance/ta948

## Connected records

- biomarkers: [IDH1 R132 mutation](https://onco.cc/biomarkers/idh1-r132/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Acute myeloid leukaemia in older or unfit patients](https://onco.cc/cancers/aml-older-unfit/), [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Chondrosarcoma](https://onco.cc/cancers/chondrosarcoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Higher-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-higher-risk/), [IDH1- and IDH2-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-idh/), [Intrahepatic cholangiocarcinoma](https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/), [Secondary and therapy-related acute myeloid leukaemia](https://onco.cc/cancers/aml-secondary/)
- technologies: [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/), [IDH inhibitors](https://onco.cc/technologies/idh-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [IDH1 / IDH2](https://onco.cc/targets/idh/), [TET2](https://onco.cc/targets/tet2/)
- companies: [CStone Pharmaceuticals](https://onco.cc/companies/cstone/), [Servier](https://onco.cc/companies/servier/)
- terms: [Crossover in trials](https://onco.cc/terms/crossover/), [Differentiation syndrome](https://onco.cc/terms/differentiation-syndrome/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/), [Metabolic theory of cancer: from Warburg to oncometabolites](https://onco.cc/terms/metabolic-theory-of-cancer/)
- trials: [AGILE](https://onco.cc/trials/agile/), [An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma](https://onco.cc/trials/nct05876754/), [An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.](https://onco.cc/trials/nct07282262/), [An Open-label Phase 3b Study of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy.](https://onco.cc/trials/nct05907057/), [Beat AML Master Trial](https://onco.cc/trials/beat-aml-master-trial/), [ClarIDHy](https://onco.cc/trials/claridhy/), [Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer](https://onco.cc/trials/nct07745296/), [Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen](https://onco.cc/trials/nct06127407/), [Lvosidenib (AK112) Combined With CapeOX and Radiotherapy in Patients With Unresectable Metastatic MSS-type Colorectal Cancer](https://onco.cc/trials/nct06593548/), [NCI-COG Pediatric MATCH (APEC1621)](https://onco.cc/trials/pediatric-match/), [SAFIR-ABC10](https://onco.cc/trials/safir-abc10/)
- pathways: [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [Mutant IDH / 2-hydroxyglutarate](https://onco.cc/pathways/idh-2hg/)
- key papers: [AGILE: ivosidenib plus azacitidine for newly diagnosed IDH1-mutated AML in patients unfit for intensive chemotherapy](https://onco.cc/key-papers/paper-agile-ivosidenib-azacitidine-nejm-2022/), [Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory acute myeloid leukaemia](https://onco.cc/key-papers/paper-ivosidenib-idh1-dinardo-nejm-2018/)
- drugs: [Oncomine Dx Target Test](https://onco.cc/drugs/oncomine-dx-target-test/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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