On December 18, 2015 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the fields of cancer metabolism and rare genetic metabolic disorders, reported the initiation of a Phase 1b, multicenter, international, open-label study of AG-221 or AG-120 in combination with induction and consolidation therapy in patients with newly diagnosed acute myeloid leukemia (AML) with an isocitrate dehydrogenase (IDH) mutation who are eligible for intensive chemotherapy. 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 (Press release, Agios Pharmaceuticals, DEC 18, 2015, View Source [SID:1234508605]). Schedule your 30 min Free 1stOncology Demo! "The five-year survival rate for AML is just 20 to 25 percent, and treatment options for newly diagnosed AML patients have not changed in decades," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "By combining a targeted therapy such as AG-221 or AG-120 with standard-of-care intensive chemotherapy in the newly diagnosed setting, we have the potential to provide significant clinical benefit early in the course of treatment."
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"Having established favorable safety profiles and durable single agent response rates for AG-221 and AG-120 in advanced AML, we believe there is a compelling case to evaluate our IDH mutant inhibitors in the frontline setting with standard of care," said Chris Bowden, M.D., chief medical officer of Agios. "Our goal is to advance AG-221 and AG-120 as rapidly as possible in a broad population in order to bring better treatment options to patients in need. This study is the first wave of our frontline strategy, with a second trial, being conducted by Celgene, combining our IDH mutant inhibitors with VIDAZA in patients not eligible for intensive chemotherapy planned for the first quarter of 2016."
About the Phase 1b Frontline Combination Trial of AG-221 or AG-120 in Newly Diagnosed AML Patients Eligible for Intensive Chemotherapy
The Phase 1b, multicenter, international, open-label clinical trial will evaluate the safety and clinical activity of AG-221 or AG-120 in combination with induction and consolidation therapy in patients with newly diagnosed AML with an IDH2 and/or IDH1 mutation who are eligible for intensive chemotherapy. The study will evaluate continuous dosing for up to one year with 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 with two types of AML induction therapies (cytarabine with either daunorubicin or idarubicin) and two types of AML consolidation therapies (mitoxantrone with etoposide [ME] or cytarabine).
The primary endpoint of the trial is to determine safety and tolerability, and the secondary endpoints include: characterization of pharmacokinetics, establishment of the recommended Phase 2 dose, and evaluation of 2-HG levels and clinical activity of the combination with standard induction. This study is open for enrollment and will include approximately twenty centers that will enroll up to 90 patients.
All patients will receive induction therapy in combination with AG-120 or AG-221. Patients who achieve a complete remission (CR), CR with incomplete platelet recovery (CRp) or CR with incomplete hematologic recovery (CRi) at the end of induction therapy will go on to receive consolidation therapy. Following consolidation therapy, patients may continue on maintenance therapy and receive daily treatment with AG-120 or AG-221 for up to one year, until relapse, development of an unacceptable toxicity or hematopoietic stem cell transplant (HSCT).