Clinical Trials

Date: 2015-12-18

Type of information: Initiation of the trial

phase: 1b

Announcement: initiation of the trial

Company: Celgene (USA - NJ) Agios Pharmaceuticals (USA -MA)

Product: AG-120 - isocitrate dehydrogenase 1 (IDH1)-mutant inhibitor, AG-221 (enasidenib)

Action mechanism:

• enzyme inhibitor/isocitrate dehydrogenase inhibitor. AG-120 is a first-in-class, orally available, selective, potent inhibitor of the mutated IDH1 (Isocitrate dehydrogenase 1) protein, and is a highly targeted investigational medicine for the treatment of patients with cancers that harbor an IDH1 mutation. Isocitrate dehydrogenase 1 and 2 are metabolic enzymes that are mutated in a wide range of hematologic and solid tumor malignancies, including acute myelogenous leukemia (AML) and glioma. Normally, IDH enzymes help to break down nutrients and generate energy for cells. When mutated, IDH creates a molecule that alters the cells’ genetic programming, and instead of maturing, the cells remain primitive and proliferate quickly.
• AG-221 is an orally available, selective, potent inhibitor of the mutated isocitrate dehydrogenase (IDH) 2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. AG-221 has received orphan drug and fast track designations from the FDA.
• AG-221 and AG-120 are part of Agios\' global strategic collaboration with Celgene. Under the terms of the collaboration, Celgene has worldwide development and commercialization rights for AG-221. Agios continues to conduct clinical development activities within the AG-221 development program and is eligible to receive up to $120 million in payments on achievement of certain milestones and royalties on net sales. For AG-120, Agios retains U.S. development and commercialization rights. Celgene has an exclusive license outside the United States . Celgene is eligible to receive royalties on net sales in the U.S. Agios is eligible to receive royalties on net sales outside the U.S. and up to $120 million in payments on achievement of certain milestones.

Disease: acute myeloid leukemia (AML)

Therapeutic area: Cancer - Oncology

Country: Germany, The Netherlands, USA

Trial details:

• The purpose of this Phase I, multicenter, clinical trial is to evaluate the safety of AG-120 and AG-221 when given in combination with standard acute myeloid leukemia induction and consolidation therapy.
• The study plans to evaluate 1 dose level of AG-120 in patients with an IDH1 mutation and 2 dose levels of AG-221 in patients with an IDH2 mutation. AG-120 or AG-221 will be administered with 2 types of acute myeloid leukemia induction therapies (cytarabine with either daunorubicin or idarubicin) and 2 types of acute myeloid leukemia consolidation therapies (mitoxantrone with etoposide [ME] or cytarabine). After consolidation therapy, patients may continue on maintenance therapy and receive daily treatment of AG-120 or AG-221 for up to 1 year from Day 1 of the first induction cycle, or until relapse, development of an unacceptable toxicity, or hematopoietic stem cell transplant (HSCT). 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). (NCT02632708)

Latest news:

• • On December 18, 2015, Agios Pharmaceuticals announced 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 . Agios's 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. A second trial is being conducted by Celgene , combining these IDH mutant inhibitors with Vidaza® in patients not eligible for intensive chemotherapy planned for the first quarter of 2016.

Is general: Yes