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Active, not recruitingNCT03173248AGILEUpdated Jun 29, 2026Results posted

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

A Phase 3 interventional study of AG-120 and Placebo in Newly Diagnosed Acute Myeloid Leukemia (AML), Untreated AML and AML Arising From Myelodysplastic Syndrome (MDS), sponsored by Institut de Recherches Internationales Servier. Active, not recruiting at 90 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-29.

Sponsored by Institut de Recherches Internationales Servier · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
146
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Study AG120-C-009 is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of AG-120 (ivosidenib) + azacitidine vs placebo + azacitidine in adult participants with previously untreated IDH1m AML who are considered appropriate candidates for non-intensive therapy. The primary endpoint is event-free survival (EFS). The key secondary efficacy endpoints are overall survival (OS), rate of complete remission (CR), rate of CR and complete remission with partial hematologic recovery (CRh), and overall response rate (ORR). Participants eligible for study treatment based on Screening assessments will be randomized 1:1 to receive oral AG-120 or matched placebo, both administered in combination with subcutaneous (SC) or intravenous (IV) azacitidine. An estimated 200 participants will take part in the study.

02

Conditions studied

  • Newly Diagnosed Acute Myeloid Leukemia (AML)
  • Untreated AML
  • AML Arising From Myelodysplastic Syndrome (MDS)
  • Leukemia, Myeloid, Acute

Keywords

  • Acute Myeloid Leukemia
  • Leukemia
  • Azacitidine
  • AG-120
  • ivosidenib
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Be ≥ 18 years of age and meet at least 1 of the following criteria defining ineligibility for intensive induction chemotherapy (IC): ≥ 75 years old, Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 2, severe cardiac disorder (e.g., congestive heart failure requiring treatment, left ventricular ejection fraction (LVEF), ≤50%, or chronic stable angina), severe pulmonary disorder (e.g., diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratory volume in 1 second ≤65%), creatinine clearance \<45 mL/minute, bilirubin >1.5 times the upper limit of normal (ULN) and/or have any other comorbidity that the Investigator judges to be incompatible with intensive IC and must be reviewed and approved by the Medical Monitor before study enrollment.
  2. Have previously untreated AML, defined according to World Health Organization (WHO) criteria, with ≥ 20% leukemic blasts in the bone marrow. Participants with extramedullary disease alone (i.e., no detectable bone marrow and no detectable peripheral blood AML) are not eligible for the study.
  3. Have an isocitrate dehydrogenase 1 (IDH1) mutation.
  4. Have an ECOG PS score of 0 to 2.
  5. Have adequate hepatic function.
  6. Have adequate renal function.
  7. Have agreed to undergo serial blood and bone marrow sampling.
  8. Be able to understand and willing to sign an informed consent form (ICF).
  9. Be willing to complete Quality of Life assessments during the study
  10. If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Females of reproductive potential, as well as fertile men and their female partners of reproductive potential, must agree to use 2 effective forms of contraception.

Exclusion criteria

Exclusion Criteria:

  1. Are candidates for and willing to receive intensive induction chemotherapy (IC) for their AML.
  2. Have received any prior treatment for AML with the exception of hydroxyurea.
  3. Have received a hypomethylating agent for myelodysplastic syndrome (MDS).
  4. Participants who had previously received an experimental agent for MDS may not be randomized until a washout period has elapsed since the last dose of that agent.
  5. Have received prior treatment with an IDH1 inhibitor.
  6. Have a known hypersensitivity to any of the components of AG-120, matched placebo, or azacitidine.
  7. Are female and pregnant or breastfeeding.
  8. Have an active, uncontrolled, systemic fungal, bacterial, or viral infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment.
  9. Have a prior history of cancer other than MDS or myeloproliferative disorder, unless the participant has been free of the disease for ≥ 1 year prior to the start of study treatment.
  10. Have had significant active cardiac disease within 6 months prior to the start of the study treatment.
  11. Have any condition that increases the risk of abnormal ECG or cardiac arrhythmia.
  12. Have a condition that limits the ingestion or absorption of drugs administered by mouth.
  13. Have uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic BP > 100 mmHg).
  14. Have clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia.
  15. Have immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
  16. Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the participant's ability to give informed consent or participate in the study.
  17. Are taking medications that are known to prolong the QT interval unless they can be transferred to other medications within ≥5 half-lives prior to dosing, or unless the medications can be properly monitored during the study. (If equivalent medication is not available, heart rate corrected QT interval [QTc] will be closely monitored.)
  18. Have a known medical history of progressive multifocal leukoencephalopathy.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
146 participants (actual)

Study arms

  • Experimental
    AG-120 + Azacitidine

    Participants received AG-120 500 mg orally, once daily (QD) in combination with azacitidine 75 milligrams per square meter per day (mg/m\^2/day) subcutaneously (SC) or intravenously (IV), on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation.

    Drug: AG-120 · Drug: Azacitidine

  • Placebo comparator
    Placebo + Azacitidine

    Participants received AG-120 matching placebo orally, QD in combination with azacitidine 75 mg/m\^2/day SC or IV, on Days 1-7, or on Days 1-5 and 8-9, of each 28-day cycle for a minimum of 6 cycles until death, disease relapse, disease progression, development of unacceptable toxicity (adverse event), confirmed pregnancy, withdrawal by participant or protocol violation .

    Drug: Placebo · Drug: Azacitidine

Interventions

  • DrugAG-120

    Tablets administered orally

    Also known as: Ivosidenib

  • DrugPlacebo

    Tablets administered orally

  • DrugAzacitidine

    Administered SC or IV

    Also known as: Vidaza®

05

What researchers measure

Primary outcomes

  1. Event-Free Survival (EFS)

    EFS was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure was defined as failure to achieve complete remission (CR) by Week 24. CR: Bone marrow blasts \<5% and no Auer rods; absence of extramedullary disease; Absolute neutrophil count (ANC) ≥1.0 × 10\^9 per litre (10\^9/L) (1000 per microlitre \[1000/μL\]); platelet count ≥100 × 10\^9/L (100,000/μL); independence of red blood cell transfusions. Participants who had an EFS event (relapse or death) after, 2 or more missing disease assessments were censored at the last adequate disease assessment documenting no relapse before the missing assessments. The reported data represents the Kaplan-Meier median value.

    Time frame: Up to Week 24

Secondary outcomes

  1. Complete Remission Rate (CR Rate)

    CR rate is defined as the proportion of participants who achieve a CR. A Cochran-Mantel-Haenszel (CMH) test will be used to compare CR rate between the 2 treatment arms.

    Time frame: Up to approximately 52 months

  2. Overall Survival (OS)

    OS is defined as the time from date of randomization to the date of death due to any cause. Kaplan-Meier (KM) curves and KM estimates of OS will be presented for each treatment arm.

    Time frame: Up to approximately 52 months

  3. CR + Complete Remission With Partial Hematologic (CRh) Rate

    CR + CRh rate is defined as the proportion of participants who achieve a CR or CRh. CRh is defined as a CR with partial recovery of peripheral blood counts (less than 5% bone marrow blasts, absolute neutrophil count (ANC) greater than 0.5 × 10\^9/liter (L) 500/microliter (μL)\], and platelets greater than 50 × 10\^9/L \[50,000/μL\]). A CMH test will be used to compare the CR + CRh rate between the 2 treatment arms.

    Time frame: Up to approximately 52 months

  4. Objective Response Rate (ORR)

    ORR is defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery \[CRp\]), partial remission (PR), and morphologic leukemia-free state (MLFS). The best response is calculated using the following hierarchy: CR, followed by CRi (including CRp), followed by PR and MLFS. A summary of best response by treatment arm will be produced. A CMH test will be used to compare ORR between the 2 treatment arms.

    Time frame: Up to approximately 52 months

  5. CR + CRi (Including CRp) Rate

    The CR + CRi (including CRp) rate is defined as the proportion of participants who achieve a CR or CRi (including CRp). A CMH test will be used to compare the CR + CRi (including CRp) rate between the 2 treatment arms.

    Time frame: Up to approximately 52 months

  6. Duration of CR (DOCR)

    DOCR will be calculated as the date of the first occurrence of CR to the date of first documented disease relapse, or death. DOCR is only defined for participants who achieve a CR.

    Time frame: Up to approximately 52 months

  7. Duration of CRh (DOCRh)

    DOCRh will be calculated as the date of the first occurrence of CR or CRh to the date of first documented disease relapse or death. DOCRh is only defined for participants who achieve a CR or CRh.

    Time frame: Up to approximately 52 months

  8. Duration of Response (DOR)

    DOR will be calculated as the date of the first response to the date of first documented disease relapse, disease progression, or death. DOR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.

    Time frame: Up to approximately 52 months

  9. Duration of CRi (DOCRi)

    DOCRi will be calculated as the date of the first occurrence of CR or CRi (including CRp) to the date of the first documented relapse or death. DOCRi is only defined for participants who achieve a CR or CRi (including CRp).

    Time frame: Up to approximately 52 months

  10. Time to CR (TTCR)

    TTCR will be assessed from the date of randomization to the date of first occurrence of CR. TTCR is only defined for participants who achieve a CR.

    Time frame: Up to approximately 52 months

  11. Time to CRh (TTCRh)

    TTCRh will be assessed from the date of randomization to the date of first occurrence of CR or CRh. TTCRh is only defined for participants who achieve a CR or CRh.

    Time frame: Up to approximately 52 months

  12. Time to Response (TTR)

    TTR will be assessed from the date of randomization to the date of the first response. TTR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.

    Time frame: Up to approximately 52 months

  13. Time to CRi (TTCRi)

    TTCRi will be assessed from the date of randomization to the date of first occurrence of CR or CRi (including CRp). TTCRi is only defined for participants who achieve a CR or CRi (including CRp).

    Time frame: Up to approximately 52 months

  14. Percentage of Participants With Abnormalities in Vital Sign Measurements

    Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.

    Time frame: Up to approximately 52 months

  15. Percentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

    Time frame: Up to approximately 52 months

  16. Percentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)

    Time frame: Up to approximately 52 months

  17. Percentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)

    LVEF is determined by ECHO or MUGA scan in participants.

    Time frame: Up to approximately 52 months

  18. Percentage of Participants With Abnormalities in Clinical Laboratory Tests

    Clinical laboratory assessments will include hematology, serum chemistry, coagulation.

    Time frame: Up to approximately 52 months

  19. Percentage of Participants With Adverse Events (AEs)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.

    Time frame: Up to approximately 52 months

  20. Percentage of Participants With AEs of Special Interest (AESIs)

    AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs include protocol-specified QT prolongation, isocitrate dehydrogenase (IDH) differentiation syndrome and leukocytosis.

    Time frame: Up to approximately 52 months

  21. Percentage of Participants With Serious Adverse Events (SAEs)

    An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    Time frame: Up to approximately 52 months

  22. Percentage of Participants With Adverse Events Leading to Discontinuation or Death

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.

    Time frame: Up to approximately 52 months

  23. Percentage of Participants Using Concomitant Medications

    Participants receiving concomitant medications will be adequately monitored by ECG controls, drug concentration (where applicable), and serum electrolytes (i.e., potassium and magnesium).

    Time frame: Up to approximately 52 months

  24. Units of Platelets and Red Blood Cells (RBC) Infused

    All measures that are indicative of clinical benefit are measured like number of units of platelet and RBC infused.

    Time frame: Up to approximately 52 months

  25. Rate of Infection

    Time frame: Up to approximately 52 months

  26. Number of Days Spent Hospitalized

    Time frame: Up to approximately 52 months

  27. Change From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire

    The EORTC QLQ-C30 questionnaire measures quality of life and consists of 30 questions that are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global quality of life; 3 symptom scales (fatigue, pain, and nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and the perceived financial burden of treatment experienced by participants with cancer.

    Time frame: Up to approximately 52 months

  28. Change From Baseline in the EORTC EQ-5D-5L Questionnaire

    The EORTC EQ-5D-5L questionnaire measures quality of life and spans 5 dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are used to build a composite of the participant's health status.

    Time frame: Up to approximately 52 months

  29. Percentage of Participants With CR With IDH1 Mutation Clearance (MC)

    CR with IDH1 MC is defined as a response of CR where there is no evidence of the IDH1 mutation by molecular techniques to below the level of detection (0.02%-0.04%) for ≥1 on-treatment time point. A CMH test will be used to compare the rate of CR between 2 treatment arms.

    Time frame: Up to approximately 52 months

  30. Percentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities

    The number of doses administered, total dose, duration of treatment, dose intensity, and the proportion of participants with dose modifications, will be summarized by treatment arm.

    Time frame: Up to approximately 52 months

  31. Circulating Plasma Concentration of AG-120

    Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.

    Time frame: Up to approximately 52 months

  32. Circulating Plasma Concentration of 2-HG

    Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.

    Time frame: Up to approximately 52 months

06

Results

Posted Mar 23, 2023

Participant flow

Participants took part in the study at 199 investigational sites from 19 March 2018 to 18 March 2021 (data cut off date). This study is ongoing. Results collected through data cut off date, 18 March 2021 are being reported.

Participant flow — Overall Study
MilestoneAG-120 + AzacitidinePlacebo + Azacitidine
Started7274
Safety analysis set7173
Completed00
Not completed7274
Withdrew: Death2846
Withdrew: Lost to follow-up01
Withdrew: Withdrawal by subject64
Withdrew: Ongoing at data cut-off date: 18 march 20213823

Outcome measures

PrimaryEvent-Free Survival (EFS)

EFS was defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure was defined as failure to achieve complete remission (CR) by Week 24. CR: Bone marrow blasts \<5% and no Auer rods; absence of extramedullary disease; Absolute neutrophil count (ANC) ≥1.0 × 10\^9 per litre (10\^9/L) (1000 per microlitre \[1000/μL\]); platelet count ≥100 × 10\^9/L (100,000/μL); independence of red blood cell transfusions. Participants who had an EFS event (relapse or death) after, 2 or more missing disease assessments were censored at the last adequate disease assessment documenting no relapse before the missing assessments. The reported data represents the Kaplan-Meier median value.

Time frame:
Up to Week 24
Reported as:
Median · months
Event-Free Survival (EFS)
monthsAG-120 + AzacitidinePlacebo + Azacitidine
Event-Free Survival (EFS)0.03 (0.03 to 11.01)0.03 (NA to NA)
Statistical analysis
  • AG-120 + Azacitidine vs Placebo + Azacitidine · Log Rank · p = 0.0011 (P-value is calculated from the one-sided log-rank test stratified by the randomization stratification factors (AML status and geographic region).) · Hazard ratio (hr): 0.33 · 95% CI 0.16 to 0.69Hazard ratio is estimated using a Cox's proportional hazards model stratified by the randomization stratification factors (AML status and geographic region) with placebo + azacitidine as the denominator.
SecondaryComplete Remission Rate (CR Rate)

CR rate is defined as the proportion of participants who achieve a CR. A Cochran-Mantel-Haenszel (CMH) test will be used to compare CR rate between the 2 treatment arms.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryOverall Survival (OS)

OS is defined as the time from date of randomization to the date of death due to any cause. Kaplan-Meier (KM) curves and KM estimates of OS will be presented for each treatment arm.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryCR + Complete Remission With Partial Hematologic (CRh) Rate

CR + CRh rate is defined as the proportion of participants who achieve a CR or CRh. CRh is defined as a CR with partial recovery of peripheral blood counts (less than 5% bone marrow blasts, absolute neutrophil count (ANC) greater than 0.5 × 10\^9/liter (L) 500/microliter (μL)\], and platelets greater than 50 × 10\^9/L \[50,000/μL\]). A CMH test will be used to compare the CR + CRh rate between the 2 treatment arms.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryObjective Response Rate (ORR)

ORR is defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery \[CRp\]), partial remission (PR), and morphologic leukemia-free state (MLFS). The best response is calculated using the following hierarchy: CR, followed by CRi (including CRp), followed by PR and MLFS. A summary of best response by treatment arm will be produced. A CMH test will be used to compare ORR between the 2 treatment arms.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryCR + CRi (Including CRp) Rate

The CR + CRi (including CRp) rate is defined as the proportion of participants who achieve a CR or CRi (including CRp). A CMH test will be used to compare the CR + CRi (including CRp) rate between the 2 treatment arms.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryDuration of CR (DOCR)

DOCR will be calculated as the date of the first occurrence of CR to the date of first documented disease relapse, or death. DOCR is only defined for participants who achieve a CR.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryDuration of CRh (DOCRh)

DOCRh will be calculated as the date of the first occurrence of CR or CRh to the date of first documented disease relapse or death. DOCRh is only defined for participants who achieve a CR or CRh.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryDuration of Response (DOR)

DOR will be calculated as the date of the first response to the date of first documented disease relapse, disease progression, or death. DOR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryDuration of CRi (DOCRi)

DOCRi will be calculated as the date of the first occurrence of CR or CRi (including CRp) to the date of the first documented relapse or death. DOCRi is only defined for participants who achieve a CR or CRi (including CRp).

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryTime to CR (TTCR)

TTCR will be assessed from the date of randomization to the date of first occurrence of CR. TTCR is only defined for participants who achieve a CR.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryTime to CRh (TTCRh)

TTCRh will be assessed from the date of randomization to the date of first occurrence of CR or CRh. TTCRh is only defined for participants who achieve a CR or CRh.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryTime to Response (TTR)

TTR will be assessed from the date of randomization to the date of the first response. TTR is only defined for participants who achieve a CR, CRi (including CRp), PR, and/or MLFS.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryTime to CRi (TTCRi)

TTCRi will be assessed from the date of randomization to the date of first occurrence of CR or CRi (including CRp). TTCRi is only defined for participants who achieve a CR or CRi (including CRp).

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Abnormalities in Vital Sign Measurements

Vital signs will include body temperature, respiratory rate, blood pressure, and heart rate.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Abnormalities in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Abnormalities in 12-lead Electrocardiograms (ECGs)
Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Abnormalities in Echocardiogram (ECHO) or Multi-Gated Acquisition (MUGA) for Left Ventricular Ejection Fraction (LVEF)

LVEF is determined by ECHO or MUGA scan in participants.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Abnormalities in Clinical Laboratory Tests

Clinical laboratory assessments will include hematology, serum chemistry, coagulation.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Adverse Events (AEs)

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With AEs of Special Interest (AESIs)

AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs include protocol-specified QT prolongation, isocitrate dehydrogenase (IDH) differentiation syndrome and leukocytosis.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Serious Adverse Events (SAEs)

An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Adverse Events Leading to Discontinuation or Death

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered an investigational medicinal product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants Using Concomitant Medications

Participants receiving concomitant medications will be adequately monitored by ECG controls, drug concentration (where applicable), and serum electrolytes (i.e., potassium and magnesium).

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryUnits of Platelets and Red Blood Cells (RBC) Infused

All measures that are indicative of clinical benefit are measured like number of units of platelet and RBC infused.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryRate of Infection
Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryNumber of Days Spent Hospitalized
Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryChange From Baseline in the European Organisation for Research and Treatment of Cancer (EORTC) QLC-C30 Questionnaire

The EORTC QLQ-C30 questionnaire measures quality of life and consists of 30 questions that are incorporated into 5 functional domains (physical, role, cognitive, emotional, and social); a global health status/global quality of life; 3 symptom scales (fatigue, pain, and nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and the perceived financial burden of treatment experienced by participants with cancer.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryChange From Baseline in the EORTC EQ-5D-5L Questionnaire

The EORTC EQ-5D-5L questionnaire measures quality of life and spans 5 dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, which are used to build a composite of the participant's health status.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With CR With IDH1 Mutation Clearance (MC)

CR with IDH1 MC is defined as a response of CR where there is no evidence of the IDH1 mutation by molecular techniques to below the level of detection (0.02%-0.04%) for ≥1 on-treatment time point. A CMH test will be used to compare the rate of CR between 2 treatment arms.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryPercentage of Participants With Drug Exposure, Dose Modifications and Dose Intensities

The number of doses administered, total dose, duration of treatment, dose intensity, and the proportion of participants with dose modifications, will be summarized by treatment arm.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryCirculating Plasma Concentration of AG-120

Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

SecondaryCirculating Plasma Concentration of 2-HG

Serial blood samples will be drawn before and after dosing of study treatment in order to determine circulating plasma concentrations.

Time frame:
Up to approximately 52 months

Results for this outcome have not been posted.

Adverse events

Collected over 3 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
AG-120 + Azacitidine27/71 (38%)49/71 (69%)68/71 (95.8%)
Placebo + Azacitidine45/73 (61.6%)60/73 (82.2%)72/73 (98.6%)
Most frequent serious events
Showing 10 of 112
Most frequent serious events
EventAG-120 + AzacitidinePlacebo + Azacitidine
Febrile neutropeniaBlood and lymphatic system disorders17/7120/73
PneumoniaInfections and infestations14/7116/73
Differentiation syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)6/711/73
PyrexiaGeneral disorders4/713/73
Pulmonary embolismRespiratory, thoracic and mediastinal disorders3/711/73
SepsisInfections and infestations1/713/73
Bronchopulmonary aspergillosisInfections and infestations2/712/73
COVID-19Infections and infestations2/710/73
ThrombocytopeniaBlood and lymphatic system disorders2/711/73
Pleural effusionRespiratory, thoracic and mediastinal disorders2/710/73
Most frequent other events
Showing 10 of 72
Most frequent other events
EventAG-120 + AzacitidinePlacebo + Azacitidine
ConstipationGastrointestinal disorders19/7138/73
NauseaGastrointestinal disorders30/7128/73
PyrexiaGeneral disorders23/7129/73
VomitingGastrointestinal disorders28/7119/73
DiarrhoeaGastrointestinal disorders25/7125/73
AstheniaGeneral disorders11/7124/73
AnaemiaBlood and lymphatic system disorders22/7121/73
HypokalaemiaMetabolism and nutrition disorders11/7121/73
NeutropeniaBlood and lymphatic system disorders20/7112/73
ThrombocytopeniaBlood and lymphatic system disorders20/7114/73

Baseline characteristics

FAS included all participants who were randomized.

Age, Continuous
Age, Continuous(years)AG-120 + AzacitidinePlacebo + AzacitidineTotal
Mean74.5 ± 6.1875.2 ± 7.3974.8 ± 6.81
Sex: Female, Male
Sex: Female, Male(Participants)AG-120 + AzacitidinePlacebo + AzacitidineTotal
Female303666
Male423880
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AG-120 + AzacitidinePlacebo + AzacitidineTotal
Hispanic or Latino617
Not Hispanic or Latino213253
Unknown or Not Reported454186
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)AG-120 + AzacitidinePlacebo + AzacitidineTotal
Race — Asian151934
Race — White121224
Race — Black or African American022
Race — Other112
Race — Not Reported444084
07

Study locations

90 sites
  • Norton Cancer Institute - Suburban
    Louisville, Kentucky 40207, United States
  • Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Royal Prince Alfred Hospital
    Camperdown, New South Wales 2050, Australia
  • Royal Adelaide Hospital
    Adelaide, South Australia 5000, Australia
  • Flinders Medical Centre
    Bedford Park, South Australia 5042, Australia
  • Salzburger Landeskliniken
    Salzburg, 5020, Austria
  • Krankenhaus Hietzing mit Neurologischem Zentrum Rosenhugel
    Vienna, 1130, Austria
  • Unicamp Universidade Estadual de Campinas
    Campinas, São Paulo 13083-878, Brazil
  • Hospital Amaral Carvalho
    Jaú, São Paulo 17210-120, Brazil
  • Instituto Nacional de Cancer
    Rio de Janeiro, 20230-130, Brazil
  • Hospital Sirio Libanes
    São Paulo, 01308-050, Brazil
  • Hospital Sao Jose
    São Paulo, 01321-001, Brazil
  • Hospital Santa Marcelina
    São Paulo, 08270-070, Brazil
  • Cancer Care Manitoba
    Winnipeg, Manitoba R3E 0V9, Canada
  • University Health Network
    Toronto, Ontario M5G 2M9, Canada
  • Henan Cancer Hospital
    Zhengzhou, Henan 450008, China
  • West China Hospital Sichuan University
    Chengdu, Sichuan 610041, China
  • Peking Union Medical College Hospital
    Beijing, China
  • Guangdong Provincial People's Hospital
    Guangzhou, 510080, China
  • The First Affiliated Hospital, College of Medicine, Zhejiang University
    Hangzhou, 310003, China
  • Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
    Tianjin, 300020, China
  • Fakultni nemocnice Ostrava
    Ostrava, Czechia
  • Hopital Haut Leveque
    Pessac, Gironde 33604, France
  • Hopital Bretonneau
    Tours, Indre-et-Loire 37044, France
  • Hotel Dieu - Nantes
    Nantes, Loire-Atlantique 44093, France
  • Centre Hospitalier Lyon Sud
    Pierre-Bénite, Rhone 69495, France
  • Centre Hospitalier Le Mans
    Le Mans, Sarthe 72037, France
  • CHRU de Brest - Hopital Morvan
    Brest, 29609, France
  • Institut dHematologie de Basse Normandie
    Caen, 14000, France
  • CHU de Grenoble
    Grenoble, 38043, France
  • Centre Hospitalier de Versailles CHV Hopital Andre Mignot
    Le Chesnay, 78 157, France
  • Groupe Hospitalier Necker Enfants Malades
    Paris, 75015, France
  • CHRU de Poitiers La Miletrie
    Poitiers, 86021, France
  • Hopital de Hautepierre
    Strasbourg, 67200, France
  • EDOG - Institut Claudius Regaud - PPDS
    Toulouse, 31059, France
  • Institut Gustave Roussy
    Villejuif, 94805, France
  • Universitatsklinikum Essen
    Essen, North Rhine-Westphalia 45122, Germany
  • Klinikum Chemnitz gGmbH
    Chemnitz, Saxony 09113, Germany
  • Charite - Universitatsmedizin Berlin
    Berlin, 13353, Germany
  • Medizinische Hochschule Hannover
    Hanover, 30625, Germany
  • Universitatsklinikum Leipzig
    Leipzig, 04103, Germany
  • LMU Klinikum der Universitat Munchen
    München, 81377, Germany
  • Universitatsklinikum Ulm
    Ulm, 89081, Germany
  • Rabin Medical Center - PPDS
    Petah Tikva, 49100, Israel
  • Kaplan Medical Center
    Rehovot, 7610000, Israel
  • Shamir Medical Center Assaf Harofeh
    Tzrifin, 70300, Israel
  • ASST dei Sette Laghi - Ospedale Di Circolo E Fondazione Macchi
    Varese, Lombardy 21100, Italy
  • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
    Meldola, 47014, Italy
  • Ospedale San Raffaele S.r.l. - PPDS
    Milan, 20132, Italy
  • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
    Milan, 20162, Italy
  • Fondazione IRCCS Policlinico San Matteo di Pavia
    Pavia, 27100, Italy
  • Ospedale Infermi di Rimini
    Rimini, 47900, Italy
  • Azienda Ospedaliera Citta della Salute e della Scienza di Torino
    Torino, 10126, Italy
  • Matsuyama Red Cross Hospital
    Matsuyama, Ehime 790-8524, Japan
  • University of Fukui Hospital
    Fukui, 910-1193, Japan
  • Japanese Red Cross Society Himeji Hospital
    Himeji, 670-8540, Japan
  • Kobe City Medical Center General Hospital
    Kobe, Japan
  • SINACOR
    Culiacán, 80230, Mexico
  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
    México, 14000, Mexico
  • VU Medisch Centrum
    Amsterdam, North Holland 1081 HV, Netherlands
  • Universitair Medisch Centrum Groningen
    Nijmegen, 6525 GA, Netherlands
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
    Wroclaw, Lower Silesian Voivodeship 50-367, Poland
  • Instytut Hematologii i Transfuzjologii
    Warsaw, Masovian Voivodeship 02-776, Poland
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, 80-214, Poland
  • Kaluga Regional Clinical Hospital
    Kaluga, 248007, Russia
  • City Clinical Hospital # 40
    Moscow, 129301, Russia
  • National Cancer Center
    Goyang-si, Gyeonggido 10408, South Korea
  • Ajou University Hospital
    Suwon, Gyeonggido 16499, South Korea
  • Pusan National University Hospital
    Busan, 602-739, South Korea
  • Severance Hospital Yonsei University Health System
    Seoul, 03722, South Korea
  • Seoul National University Hospital
    Seoul, 110-744, South Korea
  • CHUS H. Clinico U. de Santiago
    Santiago de Compostela, A Coruna 15706, Spain
  • Hospital Universitario Son Espases
    Palma de Mallorca, Balearic Islands 07010, Spain
  • Hospital Universitario Germans Trias i Pujol
    Badalona, Barcelona 08916, Spain
  • Hospital Universitario de Gran Canaria Doctor Negrin
    Las Palmas de Gran Canaria, Las Palmas 35010, Spain
  • Hospital Universitario Vall d'Hebron - PPDS
    Barcelona, 08035, Spain
  • Hospital Clinic de Barcelona
    Barcelona, 08036, Spain
  • Hospital General Universitario Gregorio Maranon
    Madrid, 28007, Spain
  • Hospital Universitario Ramon y Cajal
    Madrid, 28034, Spain
  • Hospital Universitario Fundacion Jimenez Diaz
    Madrid, 28040, Spain
  • Hospital Universitario 12 de Octubre
    Madrid, 28041, Spain
  • Hospital Universitario Virgen del Rocio - PPDS
    Seville, 41013, Spain
  • Hospital Universitari i Politecnic La Fe de Valencia
    Valencia, 46026, Spain
  • Hospital Clinico Universitario Lozano Blesa
    Zaragoza, 50009, Spain
  • Changhua Christian Medical Foundation Changhua Christian Hospital
    Changhua, 500, Taiwan
  • Kaohsiung Medical University Hospital
    Kaohsiung City, 807, Taiwan
  • China Medical University Hospital
    Taichung, 40447, Taiwan
  • Chi Mei Medical Center, Liouying
    Tainan, 736, Taiwan
  • National Taiwan University Hospital
    Taipei, Taiwan
  • Birmingham Heartlands Hospital
    Birmingham, West Midlands B9 5SS, United Kingdom
08

References and documents

Publications

  • Montesinos P, Recher C, Vives S, Zarzycka E, Wang J, Bertani G, Heuser M, Calado RT, Schuh AC, Yeh SP, Daigle SR, Hui J, Pandya SS, Gianolio DA, de Botton S, Dohner H. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2022 Apr 21;386(16):1519-1531. doi: 10.1056/NEJMoa2117344. PubMed 35443108 ↗
  • Montesinos P, Marchione DM, Recher C, Heuser M, Vives S, Zarzycka E, Wang J, Riva M, Calado RT, Schuh AC, Yeh SP, Tron AE, Hui J, Gianolio DA, Choe S, Patel P, De Botton S, DiNardo CD, Dohner H. Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed IDH1-mutated AML. Blood Adv. 2025 Oct 28;9(20):5177-5189. doi: 10.1182/bloodadvances.2025016399. PubMed 40706052 ↗
  • Woods A, Norsworthy KJ, Wang X, Vallejo J, Chiu Yuen Chow E, Li RJ, Sun J, Charlab R, Jiang X, Pazdur R, Theoret MR, de Claro RA. FDA Approval Summary: Ivosidenib in Combination with Azacitidine for Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia with an IDH1 Mutation. Clin Cancer Res. 2024 Apr 1;30(7):1226-1231. doi: 10.1158/1078-0432.CCR-23-2234. PubMed 38010220 ↗

Study documents

  • Study protocol · Oct 7, 2021
  • Statistical analysis plan · Jun 23, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03173248
Lead sponsor
Institut de Recherches Internationales Servier
Responsible party
Sponsor
First posted
Jun 1, 2017
Start date
Jun 26, 2017
Primary completion
Mar 18, 2021
Completion
Jun 30, 2026 (estimated)
Results posted
Mar 23, 2023
Last update
Jun 29, 2026

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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