Positive results from a phase 3 trial evaluating ivosidenib in combination with azacitidine in adults with previously untreated isocitrate dehydrogenase-1 (IDH1)-mutated acute myeloid leukemia (AML) showed that it met the primary and all key secondary endpoints.
The multicenter, randomized, double-blind, placebo-controlled AGILE trial (ClinicalTrials.gov Identifier: NCT03173248) evaluated the efficacy and safety of ivosidenib, an IDH1 inhibitor, plus azacitidine in 146 adults with previously untreated IDH1-mutated AML who are not candidates for intensive chemotherapy (75 years of age and older or who have comorbidities that preclude use of intensive induction chemotherapy). Patients were randomly assigned to receive either ivosidenib plus azacitidine or placebo plus azacitidine.
The primary endpoint is the event-free survival (EFS) defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Key secondary endpoints included complete remission (CR) rate, overall survival (OS), CR plus CR with partial hematologic recovery rate (CR + CRh rate), and objective response rate (ORR).
At a median follow-up of 12.4 months, results showed that treatment with ivosidenib plus azacitidine achieved a statistically significant improvement in EFS compared with placebo plus azacitidine (hazard ratio [HR], 0.33; 95% CI, 0.16-0.69; 1-sided P =.0011). The median OS was 24 months for the ivosidenib plus azacitidine arm and 7.9 months for the placebo plus azacitidine arm (HR, 0.44; 95% CI, 0.27-0.73; 1-sided P =.0005).
Additionally, the CR rate was 47.2% (n=34/72) for ivosidenib plus azacitidine vs 14.9% (n=11/74) for placebo plus azacitidine (P <.0001). The CR + CRh rate was 52.8% (n=38/72) for ivosidenib plus azacitidine vs 17.6% (n=13/74) for placebo plus azacitidine (P <.0001). The ORR was 62.5% (n=45/72) for ivosidenib plus azacitidine vs 18.9% (n=14/74) for placebo plus azacitidine (P <.0001).
Ivosidenib is currently marketed under the trade name Tibsovo and is approved for the treatment of newly-diagnosed AML with a susceptible IDH1 mutation as detected by an FDA-approved test in adults who are 75 years of age and older or who have comorbidities that preclude use of intensive induction chemotherapy. Recently, Tibsovo was approved as a targeted therapy for patients with previously treated IDH1-mutated cholangiocarcinoma.
- CStone announces results from phase 3 AGILE data of Tibsovo® (ivosidenib tablets) in combination with azacitidine for patients with previously untreated IDH1-mutated acute myeloid leukemia published in the New England Journal of Medicine. News release. CStone Pharmaceuticals. Accessed April 22, 2022. https://prnmedia.prnewswire.com/news-releases/cstone-announces-results-from-phase-3-agile-data-of-tibsovo-r-ivosidenib-tablets-in-combination-with-azacitidine-for-patients-with-previously-untreated-idh1-mutated-acute-myeloid-leukemia-published-in-the-new-england-journal-of-medicine-857567388.html
- Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. Published online April 21, 2022. doi:10.1056/NEJMoa2117344