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.
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 (eg, congestive heart failure requiring treatment, LVEF, ≤50%, or chronic
stable angina), severe pulmonary disorder (eg, 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
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 (ie, 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.
1. Are candidates for and willing to receive intensive induction chemotherapy (IC) for
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
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
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
10. Have had significant active cardiac disease within 6 months prior to the start of the
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
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
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.