Phase 3 Study Enrollment Stopped Early After Ivosidenib Combo Demonstrates Compelling Efficacy in Untreated IDH1+ AML


Combination ivosidenib/azacitidine has yielded notable improvements in survival over ivosidenib alone in IDH1-positive treatment-naïve acute myeloid leukemia.

Ivosidenib (Tibsovo) tablets in combination with azacitidine (Onureg) demonstrated an improvement in event-free survival (EFS) and overall survival (OS) over azacitidine along in patients with treatment-naïve IDH1-mutant acute myeloid leukemia (AML), according to topline data from the phase 3 AGILE trial (NCT03173248).1

Notably, the study stopped further enrollment due to the compelling efficacy data observed with ivosidenib. The regimen significantly improved EFS vs placebo plus azacitidine, meeting the primary end point of the study. Additionally, the study met several other key secondary end points, such as complete remission (CR) rate, OS, CR and CR with partial hematologic recovery (CRh), and objective response rate (ORR) superiority.

“The results of AGILE represent a major breakthrough and will be welcome news for patients dealing with previously untreated IDH1-mutated acute myeloid leukemia,” Claude Bertrand, executive vice president of R&D at Servier Group, said in a press release. “We look forward to sharing the findings from this study with the medical community and with regulatory authorities around the world.”

The global, multicenter, double-blind randomized clinical trial seeks to evaluate the safety and efficacy of combination ivosidenib and azacitidine in a population of patients with newly diagnosed disease who are not eligible for intensive chemotherapy.

Notably, 25% of patients with newly diagnosed AML who have been treated with ivosidenib have developed differentiation syndrome and less than 1% of patients with AML have developed Guillain-Barré syndrome. The most common adverse effects (AEs) associated with treatment included hemoglobin decrease (60%), fatigue (43%), arthralgia (39%), calcium decrease (39%), sodium decrease (39%), leukocytosis (38%), and diarrhea (37%). In patients with newly diagnosed AML, the most common grade 3 or higher AEs included fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolongation (11%), and diarrhea (7%).

Currently, single-agent ivosidenib is approved by the FDA for the treatment of IDH1-positive relapsed/refractory AMLand IDH1-positive newly diagnosed disease in patients who are 75 years or older and are ineligible for intensive chemotherapy.

Ivosidenib and azacitidine have previously been assessed in a population of IDH1-mutant newly diagnosed AML as part of a phase 1b study (NCT02677922) that helped to lay the foundation for the AGILE study.2

Findings from the study indicated that patients experienced an ORR of 78% (n = 18), including a CR rate of 57%, a CR with incomplete hematologic recovery/CRp rate of 13%, and a morphological leukemia-free state of 9%. The median time to response was 1.8 months and the median CR 3.5 months. Notably the median duration of response was not yet reached as of October 2018.


  1. Servier announces positive topline data from the global phase 3 study of TIBSOVO® (ivosidenib tablets) in combination with azacitidine in patients with previously untreated IDH1-mutated acute myeloid leukemia. News release. Servier. August 2, 2021.
  2. Dinardo CD, Stein AS, Stein EM, et al. Mutant IDH1 inhibitor ivosidenib (IVO; AG-120) in combination with azacitidine (AZA) for newly diagnosed acute myeloid leukemia (ND AML). J Clin Oncol. 2019;37(15):7011-7011. doi:10.1200/JCO.2019.37.15_suppl.7011
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