Treatment with ivosidenib tablets in combination with azacitidine led to improvement in event-free survival in patients with previously untreated IDH1-mutated acute myeloid leukemia, meeting the primary end point of the phase 3 AGILE study.
Treatment with ivosidenib tablets (Tibsovo) in combination with azacitidine led to improvement in event-free survival (EFS) in patients with previously untreated IDH1-mutated acute myeloid leukemia (AML), meeting the primary end point of the phase 3 AGILE study.
According to a press announcement by Servier, the developer of ivosidenib, the EFS improvement met the criterion for statistical significance. The key secondary end point of complete remission (CR) rate, overall survival, CR with partial hematologic recovery rate, and complete response rate were also achieved.
"Acute myeloid leukemia has a poor prognosis, especially for newly diagnosed patients who are not eligible for intensive chemotherapy," said Susan Pandya, MD, vice president of Clinical Development, Servier Pharmaceuticals, in a statement. "Tibsovo monotherapy has been instrumental in transforming outcomes for adult patients with newly diagnosed or relapsed refractory AML harboring an IDH1 mutation. These promising results from the AGILE study support the added benefit of inhibiting the mutant IDH1 enzyme in combination with standard chemotherapy in the newly diagnosed intensive chemotherapy ineligible setting. We look forward to presenting the full results of the AGILE trial to show how Tibsovo in combination with azacitidine may improve outcomes in previously untreated patients with IDH1-mutated acute myeloid leukemia."
It was recently recommended by an Independent Data Monitoring Committee that enrollment to the AGILE study be halted considering a notable difference in the clinical importance observed between the ivosidenib plus azacitidine treatment arm and placebo and azacitidine treatment arm. Full results from the study will be presented at an upcoming medical congress.
"The results of AGILE represent a major breakthrough and will be welcome news for patients dealing with previously untreated IDH1-mutated acute myeloid leukemia," said Claude Bertrand, executive vice president of Research and Development at the Servier Group, in the press release. "We look forward to sharing the findings from this study with the medical community and with regulatory authorities around the world."
The ongoing multicenter, double-blind, randomized, placebo-controlled study is investigating the experimental combination of ivosidenib and azacitidine in approximately 148 patients with treatment-naïve IDH1-mutated AML. Patients in the ivosidenib receive the agent a 500 mg orally once daily in combination azacitidine 75 mg/m2/day given either by subcutaneous of intravenous infusion for the first week of each cycle. In the control arm, patients received matching doses of placebo and azacitidine.
Pending the reopening of enrollment to the study, eligible patients are those aged 18 years or older with IDH1-mutant AML, an ECOG performance status of 2 or lower, and adequate hepatic and renal function.
Ivosidenib is already an FDA-approved therapy for adults with IDH1-mutant relapsed or refractory AML and newly diagnosed IDH1-mutant AML who are ≥ 75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. There remains an unmet medical need for an effective combination therapy for patents with previously untreated IDH1-mutant AML. Outside of AML, the FDA granted priority review to a new drug application for ivosidenib as a potential therapy for patients with previously treated IDH1-mutated cholangiocarcinoma
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. Accessed August 2, 2021. https://bit.ly/37hJODg