Long-term follow-up confirms the sustained efficacy of ivonib/tosuvo in IDH1-mutated AML

New long-term follow-up data from the pivotal Phase 3 AGILE trial (NCT03173248) highlights the importance of Ivosid enib) combined with azacitidine in patients with newly diagnosed isocitrate dehydrogenase 1 (IDH1)-mutated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. These findings further confirm that ivonib plus azacitidine is the standard of care for this patient population, addressing a critical need to improve outcomes in a population with a historically poor prognosis.

As ofJune 2022, a post hoc analysis with a median follow-up time of 28.6 months showed that patients treated withivoniband azacitidine had significantly longer median overall survival (OS). Median OS was 29.3 months (95% CI, 13.2-not reached) in the ivonib combination group compared with 7.9 months (95% CI, 4.1-11.3) in the placebo-azacitidine group (HR, 0.42; 95% CI, 0.27-0.65; P<0.0001). This sustained survival benefit is consistent with and further strengthens previously reported results.

In addition to overall survival, long-term data showed faster and more durable hematologic recovery in the ivosidenib group. Of note, 53.8% of patients treated with ivosidenib achieved transfusion independence, which was significantly higher than the 17.1% observed in the placebo azacitidine group (P=0.0004). 1 Additionally, on Day 1 of Cycle 14, 30.3% (10 of 33 evaluable patients) of the ivosidenib arm achieved negativity for molecularly measurable residual disease (MRD), with all patients having a complete response (CR). Seven of these patients achieved MRD negativity on day 1 of cycle 7, highlighting early and deep responses.

The safety profile of ivonib combined with azacitidine was consistent with previously published data, and no new or unexpected safety signals emerged during long-term follow-up. The most common grade ≥3 hematologic adverse events (AEs) included anemia (26.4%), neutropenia (30.6%), and febrile neutropenia (27.8%). Among non-hematologic adverse events, the most commonly reported grade ≥3 events were electrocardiographic QT interval prolongation (11.1%), pneumonitis (22.2%), nausea (2.8%), hypokalemia (2.8%), and pyrexia (2.8%). These findings underscore the therapy's safety in a vulnerable patient population.

The AGILE trial (NCT03173248) is a global, multicenter, double-blind, randomized, placebo-controlled Phase 3 study. The study was designed to evaluate the efficacy and safety of ivonib plus azacitidine versus placebo plus azacitidine in previously untreated IDH1-mutant AML who are not candidates for intensive chemotherapy. The primary endpoint of the study is event-free survival, and key secondary endpoints include CR rate, OS and objective response rate.

AML is a rapidly progressive cancer of the blood and bone marrow and is the most common acute leukemia in adults. The 5-year survival rate of AML remains challenging at approximately 31.9%. For 6% to 10% of AML patients, mutations in the IDH1 enzyme prevent normal hematopoietic stem cell differentiation, leading to the development of leukemia. Targeting this specific mutation with drugs like ivonib offers a precision medicine approach to these patients.

In May 2022, the U.S. Food and Drug Administration approved ivonib in combination with azacitidine for adults 75 years of age or older with newly diagnosed IDH1-mutant acute myeloid leukemia or patients with comorbidities that preclude intensive induction chemotherapy. This approval is under Priority Review and the Real-Time Oncology Review (RTOR) pilot program, underscoring the urgency of quickly delivering safe and effective treatments to patients. These long-term results further confirm the clinical utility of ivonib in a population that has historically faced significant challenges with treatment and prognosis.

Reference: https://www.targetedonc.com/view/long-term-follow-up-affirms-ivosidenib-s-sustained-benefit-in-idh1-mutated-aml