On December 10, 2022 Servier, a leader in oncology committed to bringing the promise of tomorrow to the patients we serve, reported new data at the 64th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) characterizing clonal evolution and relapse mechanisms in patients with newly-diagnosed IDH1-mutated acute myeloid leukemia (AML) who are 75 years of age or older or have comorbidities that preclude use of intensive induction chemotherapy treated with TIBSOVO in combination with azacitidine (Press release, Servier, DEC 10, 2022, View Source [SID1234625039]).

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Results from the study reinforce that TIBSOVO in combination with azacitidine leads to deep, durable remissions associated with clearance of IDH1-mutated AML, with no second-site IDH1 mutations observed to date amongst the patients enrolled in the TIBSOVO plus azacitidine study arm with both baseline and longitudinal DNA sequencing available (46/72 patients). Amongst patients who relapsed (n=22), mutations in other genes, including IDH2, can emerge and provide an opportunity for relapse. Further study is needed to better characterize mechanisms of relapse for patients treated with TIBSOVO plus azacitidine combination therapy.

"Combination therapy consisting of TIBSOVO in combination with azacitidine for newly-diagnosed patients with acute myeloid leukemia and an IDH1 mutation has shown significant clinical effectiveness, but it’s important that we analyze patient response throughout their treatment to better understand mechanisms of resistance," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "We are committed to our exploratory translational efforts and will continue to update the data, as available, to contribute to a better understanding of how to improve outcomes for patients living with this aggressive hematologic malignancy."

These data presented today at ASH (Free ASH Whitepaper) 2022 represent continued clinical evidence on the effectiveness of TIBSOVO amongst newly-diagnosed AML patients with an IDH1 mutation who are 75 years of age or older or have comorbidities that preclude use of intensive induction chemotherapy, and follows the expanded approval of TIBSOVO in AML supported by data from the AGILE study. Data from the global Phase 3 AGILE study showed TIBSOVO as the first IDH1 mutation-specific targeted therapy to demonstrate improved event-free survival (EFS) and overall survival (OS) in combination with azacitidine compared to azacitidine plus placebo.

"These new data reinforce the original results from the AGILE trial, showing TIBSOVO in combination with azacitidine as an effective, first-of-its kind combination treatment option for patients with newly-diagnosed, IDH1-mutated acute myeloid leukemia," said Eytan Stein, M.D., Chief of the Leukemia Service in the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center (MSKCC). "Given the rapid progression of acute myeloid leukemia, it’s important to have a targeted therapeutic option that provides significant event-free survival and overall survival alongside a favorable safety profile, and that’s what we’ve seen clinically with TIBSOVO plus azacitadine."

About the NCT03173248 AGILE Phase 3 AML Triali

The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy). The study’s primary endpoint is event-free survival (EFS), defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24.

Key secondary endpoints include CR rate, defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS).

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults, with approximately 20,000 new cases in the U.S., and 43,000 cases in Europe each year.ii,iii AML incidence significantly increases with age, and the median age of diagnosis is 68.ii The five-year survival rate is approximately 30.5%.iv For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia.v

About TIBSOVO (ivosidenib tablets)

TIBSOVO (ivosidenib tablets) is approved in the U.S. in combination with azacitidine for the treatment of patients with newly-diagnosed IDH1-mutated acute myeloid leukemia (AML) in adults 75 years of age or older, or who have comorbidities that preclude use of intensive induction chemotherapy. TIBSOVO is the first therapy targeting cancer metabolism approved in combination with azacitidine for patients with newly-diagnosed IDH1-mutated AML.

TIBSOVO is also approved in the U.S. as monotherapy for the treatment of adults with IDH1-mutant relapsed or refractory AML, and for adults with newly-diagnosed IDH1-mutated AML who are ≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy. Last year, TIBSOVO garnered its first approval in a non-hematologic malignancy for patients with previously treated IDH1-mutated cholangiocarcinoma.

Please see the TIBSOVO indications and Important Safety Information with a link to the full Prescribing Information below.