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Evaluating AG-120 for patients with advanced blood cancers and IDH1 mutations

A Phase I, Multicenter, Open-Label, Dose-Escalation and Expansion, Safety, Pharmacokinetic, Pharmacodynamic, and Clinical Activity Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

Phase 1 Interventional Servier · NCT02074839

This study is testing a new drug called AG-120 to see if it can help people with advanced blood cancers that have a specific IDH1 mutation feel better and live longer.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment291 (estimated)
Ages18 Years and up
SexAll
SponsorServier Industry-sponsored
Locations30 sites (Birmingham, Alabama and 29 other locations)
Trial IDNCT02074839 on ClinicalTrials.gov

What this trial studies

This Phase I multicenter study aims to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-120 in patients with advanced hematologic malignancies that have an IDH1 mutation. The study consists of a dose escalation phase to determine the maximum tolerated dose, followed by a dose expansion phase to further evaluate the recommended dose's safety and efficacy. Additionally, a substudy will focus on patients with relapsed or refractory myelodysplastic syndrome with the same mutation. Participants will be monitored until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with documented IDH1 R132 gene mutations and advanced hematologic malignancies.

Not a fit: Patients without IDH1 mutations or those with severe comorbidities that prevent participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced hematologic malignancies harboring IDH1 mutations.

How similar studies have performed: Previous studies targeting IDH1 mutations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Subject must be ≥18 years of age.
* Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation.
* Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
* Subjects must have ECOG PS of 0 to 2.
* Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed).
* Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic disease
* Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or creatinine clearance \>40mL/min based on Cockroft-Gault glomerular filtration rate (GFR)
* Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
* Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration.

Key Exclusion Criteria:

* Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin GVHD is permitted.)
* Subjects who received systemic anticancer therapy or radiotherapy \<14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120).
* Subjects who received an investigational agent \<14 days prior to their first day of study drug administration.
* Subjects who are pregnant or breastfeeding.
* Subjects with an active severe infection or with an unexplained fever \>38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled).
* Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1.
* Subjects with a history of myocardial infarction within the last 6 months of screening.
* Subjects with a known unstable or uncontrolled angina pectoris.
* Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.
* Subjects with known unstable or uncontrolled angina pectoris.
* Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events.
* Patients taking medications that are known to prolong the QT interval
* Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C.
* Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
* Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.

Where this trial is running

Birmingham, Alabama and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Relapsed or Refractory Acute Myeloid LeukemiaUntreated AMLOther IDH1-mutated Positive Hematologic MalignanciesMyelodysplastic Syndromesacute myeloid leukemiaAMLmyelodysplastic syndromeMDS
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.