On March 30, 2016 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the initiation of a Phase 1/2, multicenter, international, open-label study, sponsored by Celgene Corporation, of AG-221 or AG-120 in combination with VIDAZA (azacitidine for injection) in patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase (IDH) mutation who are not eligible for intensive chemotherapy (Press release, Agios Pharmaceuticals, MAR 30, 2016, View Source [SID:1234510125]). Schedule your 30 min Free 1stOncology Demo! AG-221 and AG-120 are first-in-class, oral, selective, potent inhibitors of mutant IDH2 and IDH1, respectively, and are being developed in collaboration with Celgene.
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"Many newly diagnosed AML patients cannot tolerate intensive chemotherapy, which limits their available treatment options," said Anthony S. Stein, M.D., study investigator and co-director of the leukemia program at City of Hope Cancer Center. "Based on the safety and efficacy demonstrated in clinical studies of AG-221 and AG-120 in relapsed / refractory AML, there is potential to provide a new treatment option for newly diagnosed IDH mutant AML patients by combining these therapies with VIDAZA in the frontline setting."
"We are rapidly executing our frontline strategy for our IDH inhibitors, having now initiated a second study in newly diagnosed AML patients," said Chris Bowden, M.D., chief medical officer of Agios. "By combining AG-221 or AG-120 with VIDAZA at the onset of diagnosis, we hope to demonstrate benefit for patients with IDH mutant AML who are not eligible for intensive chemotherapy."
About the Phase 1/2 Frontline Combination Trial of AG-221 or AG-120 with VIDAZA in Newly Diagnosed AML Patients Not Eligible for Intensive Chemotherapy
The Phase 1/2, multicenter, international, open-label clinical trial will evaluate the safety and clinical activity of AG-221 or AG-120 in combination with VIDAZA in patients with newly diagnosed AML with an IDH2 and/or IDH1 mutation who are not eligible for intensive chemotherapy. The study consists of a Phase 1b dose-escalation stage and a Phase 2 randomized stage.
The study will evaluate AG-221 administered at an initial oral dose of 100 mg once daily in patients with an IDH2 mutation or AG-120 administered at an initial oral dose of 500 mg once daily in patients with an IDH1 mutation. AG-221 or AG-120 will be administered continuously in a 28-day cycle with VIDAZA at the standard 75 mg/m2 daily dose for 7 days of each 28-day cycle.
The primary endpoint of the Phase 1b stage of the trial is to determine safety and tolerability and to establish the recommended Phase 2 dose of AG-221 or AG-120 in combination with VIDAZA. The primary endpoint of the Phase 2 stage of the trial is to determine the efficacy of the combination of AG-221 or AG-120 with VIDAZA compared with VIDAZA alone. Secondary endpoints include evaluation of safety, characterization of pharmacokinetics and evaluation of effects on health-related quality-of-life outcomes. This study will enroll up to 150 patients.
Please refer to www.clinicaltrials.gov for additional clinical trial details.
About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and according to the American Cancer Society, the median age of onset is 66. Less than 10 percent of U.S. AML patients are eligible for bone marrow transplant, and the vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 20 to 25 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases. IDH2 mutations are present in about 9 to 13 percent of AML cases.
About IDH Mutations and Cancer
IDH1 and IDH2 are two metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies, including AML. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH increases production of an oncometabolite 2-hydroxyglutarate (2HG) that alters the cells’ epigenetic programming, thereby promoting cancer. 2HG has been found to be elevated in several tumor types. Agios believes that inhibition of the mutated IDH proteins may lead to clinical benefit for the subset of cancer patients whose tumors carry them.