marked.bio

IDH1 inhibitor · small molecule

ivosidenib

27 active trials across 3 of our biomarkers, targeting IDH1. 7 active approvals for a biomarker on marked.bio.

Also known as AG-120, Tibsovo.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
ivosidenib with azacitidine
FDA, 2022
newly diagnosed, susceptible IDH1 mutation, age >=75 or unfit for intensive chemotherapy FDA approval 25/05/2022. Source
EU (EMA), 2023
newly diagnosed, IDH1 R132 mutation, not eligible for standard induction chemotherapy EU marketing authorisation 04/05/2023. Source
Tibsovo 		IDH1/2 mutation AML Approved 2022 Approved 2023

AGILE (AG120-C-009) vs placebo + azacitidine, 72 vs 74 patients
EFS HR 0.35 (0.17-0.72)CR 47% vs 15%OS 24.0 months vs 7.9 months, HR 0.44 (0.27-0.73)

Trial details and side effects
Patients
newly diagnosed IDH1-mutant AML unfit for intensive chemotherapy (NCT03173248)
Most common side effects
diarrhoea, fatigue, oedema, nausea, vomiting, decreased appetite, leukocytosis, arthralgia, dyspnoea, abdominal pain, mucositis, rash, QT prolongation, differentiation syndrome
Notes
FDA approval summary (2022); side effects are those in 25% or more of patients across ivosidenib trials.
Source
FDA approval summary
ivosidenib
FDA, 2018
relapsed or refractory, susceptible IDH1 mutation FDA approval 20/07/2018; companion test Abbott RealTime IDH1 Assay. Boxed warning: differentiation syndrome. Source
FDA, 2019
newly diagnosed, susceptible IDH1 mutation, age >=75 or unfit for intensive chemotherapy (monotherapy) FDA approval 02/05/2019. Source
Tibsovo 		IDH1/2 mutation AML Approved 2018 Not approved

AG120-C-001 single-arm, 174 patients
CR+CRh 33% (26-40)Lasting 8.2 months

Trial details and side effects
Patients
relapsed or refractory IDH1-mutant AML (NCT02074839)
Most common side effects
fatigue, leukocytosis, arthralgia, diarrhoea, dyspnoea, oedema, nausea, mucositis, QT prolongation, rash, pyrexia, cough, constipation
Notes
FDA approval summary (2018); side effects are those in 20% or more of patients. Differentiation syndrome can be fatal.
Source
FDA approval summary
ivosidenib
FDA, 2023
relapsed or refractory myelodysplastic syndromes, susceptible IDH1 mutation FDA approval 24/10/2023. Source
Tibsovo 		IDH1/2 mutation MDS Approved 2023 Not approved

AG120-C-001 (MDS) single-arm, 18 patients
CR 39% (17-64)Lasting not reached

Trial details and side effects
Patients
relapsed or refractory IDH1-mutant MDS (NCT02074839)
Most common side effects
diarrhoea, constipation, mucositis, nausea, arthralgia, fatigue, cough, myalgia, rash
Notes
FDA approval summary (2023). All responses were complete remissions.
Source
FDA approval summary
ivosidenib
FDA, 2021
previously treated, locally advanced or metastatic, IDH1 mutation FDA approval 25/08/2021. Source
EU (EMA), 2023
locally advanced or metastatic, IDH1 R132 mutation, after >=1 prior line of systemic therapy EU marketing authorisation 04/05/2023. Source
Tibsovo 		IDH1/2 mutation cholangiocarcinoma Approved 2021 Approved 2023

In the US approval report

ClarIDHy vs placebo, 185 randomised
PFS HR 0.37 (0.25-0.54)OS HR 0.79 (0.56-1.12), not significant (about 70% of placebo patients crossed over)

Trial details and side effects
Patients
previously treated IDH1-mutant cholangiocarcinoma (NCT02989857)
Most common side effects
fatigue, nausea, abdominal pain, diarrhoea, cough, decreased appetite, ascites, vomiting, anaemia, rash
Notes
FDA approval as reported by ASCO Post (2021); median PFS was 2.7 vs 1.4 months in the published trial. Side effects are those in 15% or more of patients.
Source
US approval report

In the EU summary (EPAR)

ClarIDHy vs placebo, 187 patients
PFS 2.7 months vs 1.4 months, HR 0.37 (0.25-0.54)OS 10.3 months vs 7.5 months, HR 0.79 (0.56-1.12), not significant (about 70% of placebo patients crossed over)

Trial details and side effects
Patients
previously treated IDH1-mutant cholangiocarcinoma (NCT02989857)
Most common side effects
fatigue, nausea, abdominal pain, diarrhoea, cough, decreased appetite, ascites, vomiting, anaemia, rash
Notes
EU figures from the EPAR summary; trial details and side effects from the US approval.
Source
EU summary (EPAR)

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
IDH1/2 mutation 27 38 Phase 3
FLT3 mutation (ITD/TKD) 1 2 Phase 1
FGFR2 fusion or rearrangement 0 1 –

Sponsors

Industry sponsors leading active biomarker-selected trials of ivosidenib.

  1. Servier Affaires Médicales 2
  2. Servier Bio-Innovation 1

Trials

27 of 38 trials shown

  1. Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen

    Recruiting Phase 3 Servier Bio-Innovation Started 2024Primary completion 2028-02 NCT06127407

    ivosidenib FDA EU

    Have documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available that …

    IDH1/2 mutationLocally Advanced or Metastatic Conventional Chondrosarcoma With an IDH1 Mutation, Untreated or Previously Treated With 1 Systemic Treatment Regimen

  2. Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation

    Recruiting Phase 3 Institut de Recherches Internationales Servier Started 2024Primary completion 2027-11 NCT06465953

    ivosidenib FDA EUazacitidine

    Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to WHO criteria (5th edition):

    IDH1/2 mutationHypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes (MDS)

  3. An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

    Active, not recruiting Phase 3 Servier Affaires Médicales Started 2023Primary completion 2027-12 NCT05876754

    ivosidenib FDA EU

    Have a documented IDH1 R132C, R132L, R132G, R132H, or R132S gene-mutated disease

    IDH1/2 mutationCholangiocarcinoma

  4. 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.

    Recruiting Phase 3 Servier Affaires Médicales Started 2023Primary completion 2027-10 NCT05907057

    ivosidenib FDA EUazacitidine

    Have a documented IDH1 R132 gene-mutated disease

    IDH1/2 mutationAcute Myeloid Leukemia (AML)

  5. A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy

    Active, not recruiting Phase 3 Stichting Hemato-Oncologie voor Volwassenen Nederland Started 2019Primary completion 2027-04 NCT03839771

    ivosidenib FDA EUenasidenib FDA

    Newly diagnosed AML or MDS-EB2 defined according to WHO criteria, with a documented IDH1 or IDH2 gene mutation (as determined by the clinical trial assay) at a specific site (IDH1 R132, IDH2 R140, IDH…

    IDH1/2 mutationAcute Myeloid Leukemia, Myelodysplastic Syndrome With Excess Blasts-2

  6. Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation

    Active, not recruiting Phase 3 Institut de Recherches Internationales Servier Started 2017Primary completion 2021-03 NCT03173248

    ivosidenib FDA EUazacitidine

    Have an isocitrate dehydrogenase 1 (IDH1) mutation.

    IDH1/2 mutationNewly Diagnosed Acute Myeloid Leukemia (AML), Untreated AML, AML Arising From Myelodysplastic Syndrome (MDS), Leukemia, Myeloid, Acute

  7. Oral Decitabine Plus Ivosidenib as First Line for Older/Unfit Adult AML Patients

    Recruiting Phase 2 PETHEMA Foundation Started 2026Primary completion 2029-04 NCT07507760

    decitabineivosidenib FDA EUHydroxyureacytarabine

    IDH1 R132 mutations (centrally assessed by PCR and NGS).

    IDH1/2 mutationAcute Myeloid Leukemia With Gene Mutations

  8. Study Evaluating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy.

    Not yet recruiting Phase 2 French Innovative Leukemia Organisation Started 2026Primary completion 2030-09 NCT07463768

    ivosidenib FDA EUazacitidine

    Presence of IDH1 R132 mutation at AML diagnosis

    IDH1/2 mutationAcute Myeloid Leukemia

  9. Ivosidenib as Post-HSCT Maintenance for AML

    Recruiting Phase 2 Massachusetts General Hospital Started 2026Primary completion 2028-01 NCT06707493

    ivosidenib FDA EU

    IDH1 mutations could have been detected by any mutational technique at any prior point including at diag…

    IDH1/2 mutationIDH1 Mutation, Acute Myeloid Leukemia (AML), Hematopoietic Stem Cell Transplant (HSCT)

  10. A Study of the Combination of Ivosidenib, Azacitidine, and Venetoclax Followed by Ivosidenib Alone in People With Acute Myeloid Leukemia

    Recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2026Primary completion 2028-01 NCT07392242

    ivosidenib FDA EUazacitidinevenetoclax

    Participant has IDH1-R132 mutation present prior to initiating Ivo/Aza/Ven confirmed by CLIA approved local testing…

    IDH1/2 mutationAcute Myeloid Leukemia

  11. Ivosidenib as Maintenance Therapy in Transplant-Ineligible IDH1-mutated AML and HR-MDS

    Recruiting Phase 2 Ruijin Hospital Started 2026Primary completion 2027-05 NCT07607418

    ivosidenib FDA EU

    Molecularly confirmed diagnosis of IDH1-mutated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).

    IDH1/2 mutationAML (Acute Myeloid Leukemia), MDS (Myelodysplastic Syndrome)

  12. Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML

    Recruiting Phase 1/2 Institute of Hematology & Blood Diseases Hospital Started 2025Primary completion 2026-10 NCT06611839

    ivosidenib FDA EUvenetoclaxazacitidine

    Venetoclax in Combination With Ivosidenib and Azacitidine for Newly Diagnosed IDH1-Mutated AML

    IDH1/2 mutationAML, IDH1 Mutation, Treatment

  13. a New Treatment of Newly Diagnosed IDH1 Mutation Acute Myeloid Leukemia

    Recruiting Phase 2 The First Affiliated Hospital of Soochow University Started 2025Primary completion 2026-04 NCT07007949

    ivosidenib FDA EUvenetoclaxazacitidine

    a New Treatment of Newly Diagnosed IDH1 Mutation Acute Myeloid Leukemia

    IDH1/2 mutationAcute Myeloid Leukemia, IDH1 Gene Mutation, Ivosidenib

  14. Prospective Evaluation of Ivosidenib Maintenance Following Allogeneic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Neoplasia With IDH1 (Isocitrate Dehydrogenase 1) Mutation

    Recruiting Phase 2 Technische Universität Dresden Started 2025Primary completion 2029-10 NCT06717958

    ivosidenib FDA EU

    AML or MDS with IDH1 mutation

    IDH1/2 mutationAML, MDS

  15. Phase II Study Evaluating Ivosidenib Maintenance After SOC Adjuvant Chemotherapy in Curative mIDH1 Cholangiocarcinoma

    Recruiting Phase 2 Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest Started 2025Primary completion 2030-12 NCT07260175

    ivosidenib FDA EU

    …se II Study Evaluating Ivosidenib Maintenance After SOC Adjuvant Chemotherapy in Curative mIDH1 Cholangiocarcinoma

    IDH1/2 mutationCholangiocarcinoma, IDH Mutation

  16. 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.

    Recruiting Phase 2 Peking Union Medical College Hospital Started 2024Primary completion 2026-10 NCT07282262

    ivosidenib FDA EUlenvatinibPD-1/PD-L1 inhibitor

    Genetic Mutation: Presence of an IDH1 mutation confirmed by genetic testing.

    IDH1/2 mutationBiliary Tract Cancer

  17. IDH Targeted/Non- Targeted vs Non-targeted/IDH-targeted Approaches in the Treatment of Newly Diagnosed IDH Mutated AML Patients Not Candidates for Intensive Induction Therapy (I- DATA Study)

    Recruiting Phase 2 Alice Mims Started 2022Primary completion 2027-09 NCT05401097

    azacitidineenasidenib FDAivosidenib FDA EUvenetoclax

    Patients with newly diagnosed IDH1 or IDH2 mutated AML

    IDH1/2 mutationAcute Myeloid Leukemia

  18. Decitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

    Recruiting Phase 1/2 M.D. Anderson Cancer Center Started 2021Primary completion 2027-11 NCT04774393

    decitabineenasidenib FDAivosidenib FDA EUvenetoclax

    Subjects must have documented IDH1 or IDH2 gene mutation

    IDH1/2 mutationAcute Myeloid Leukemia, Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

  19. AG-120 in People With IDH1 Mutant Chondrosarcoma

    Active, not recruiting Phase 2 Memorial Sloan Kettering Cancer Center Started 2020Primary completion 2027-03 NCT04278781

    ivosidenib FDA EU

    Have a documented IDH1 gene mutation (from a fresh tumor biopsy or from archived tumor tissue) confirmed by a CLIA approved la…

    IDH1/2 mutationChondrosarcoma, Chondrosarcoma, Grade 2, Chondrosarcoma, Grade 3, IDH1 Gene Mutation

  20. Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

    Active, not recruiting Phase 2 National Cancer Institute (NCI) Started 2020Primary completion 2025-03 NCT04195555

    ivosidenib FDA EU

    … in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)

    IDH1/2 mutationRecurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Langerhans Cell Histiocytosis

  21. CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    Recruiting Phase 2 M.D. Anderson Cancer Center Started 2020Primary completion 2028-06 NCT04493164

    ivosidenib FDA EUdaunorubicincytarabineCPX-351

    IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e.

    IDH1/2 mutationAcute Myeloid Leukemia With Gene Mutations, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Recurrent Acute Myeloid Leukemia

  22. IDH1 (AG 120) Inhibitor in Patients With IDH1 Mutated Myelodysplastic Syndrome

    Active, not recruiting Phase 2 Groupe Francophone des Myelodysplasies Started 2019Primary completion 2027-04 NCT03503409

    ivosidenib FDA EU

    Presence of IDH1 mutation in either blood or marrow prior to start of therapy;

    IDH1/2 mutationMyelodysplastic Syndromes, Acute Myeloid Leukemia

  23. Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies

    Recruiting Phase 1/2 M.D. Anderson Cancer Center Started 2018Primary completion 2027-09 NCT03471260

    azacitidineivosidenib FDA EUvenetoclax

    IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e.

    IDH1/2 mutationAcute Myeloid Leukemia, Hematopoietic and Lymphoid System Neoplasm, Myelodysplastic Syndrome, Myeloproliferative Neoplasm

  24. Ivosidenib and Ruxolitinib in Patients With Advanced Myeloproliferative Neoplasms (MPNs) That Have an IDH1 Gene Mutation

    Recruiting Phase 1 University of Chicago Started 2024Primary completion 2029-05 NCT06291987

    ivosidenib FDA EURuxolitinib

    Advanced-Phase IDH1-mutated Ph-negative MPNs (both untreated and relapsed/refractory) including any of the following:

    IDH1/2 mutationMyeloproliferative Neoplasms

  25. A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)

    Active, not recruiting Phase 1 Memorial Sloan Kettering Cancer Center Started 2023Primary completion 2027-04 NCT05756777

    gilteritinibivosidenib FDA EUenasidenib FDA

    Patient has relapsed or refractory AML with dually mutant IDH2/FLT3, IDH1/FLT3 (ITD or TKD) , or other FLT3 mutation sensitive to gilteritinib.

    IDH1/2 mutationFLT3 mutation (ITD/TKD)Acute Myeloid Leukemia (AML)

  26. Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation

    Active, not recruiting Phase 1 Institut de Recherches Internationales Servier Started 2015Primary completion 2018-12 NCT02632708

    ivosidenib FDA EUenasidenib FDAcytarabinedaunorubicinidarubicinmitoxantroneetoposide

    …e promyelocytic leukemia (APL) \[AML with t(15;17)\], with locally documented IDH1 and/or IDH2 gene mutation scheduled for induction therapy followed by consolidation therapy.

    IDH1/2 mutationNewly Diagnosed Acute Myeloid Leukemia (AML), Untreated AML, AML Arising From Myelodysplastic Syndrome (MDS), AML Arising From Antecedent Hematologic Disorder (AHD)

  27. Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

    Recruiting Phase 1 Institut de Recherches Internationales Servier Started 2014Primary completion 2026-12 NCT02074839

    ivosidenib FDA EU

    Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation.

    IDH1/2 mutationRelapsed or Refractory Acute Myeloid Leukemia (AML), Untreated AML, Other IDH1-mutated Positive Hematologic Malignancies, Myelodysplastic Syndromes