Clinical Trials

Date: 2017-06-24

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results at the 22nd Congress of the European Hematology Association (EHA)

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

Product: Idhifa® (enasidenib)

Action mechanism:

• enzyme inhibitor/isocitrate dehydrogenase inhibitor. Enasidenib (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 is  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.

Disease: relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On June 24, 2017, Agios Pharmaceuticals announced new efficacy and safety data from the ongoing Phase 1/2 dose-escalation and expansion study evaluating Idhifa® (enasidenib) in patients with relapsed or refractory acute myeloid leukemia and an isocitrate dehydrogenase-2 (IDH2) mutation. These data have been presented in an oral session at the 22nd Congress of the European Hematology Association (EHA).
• As of October 14, 2016, a total of 345 patients with advanced hematologic malignances and an IDH2 mutation were enrolled into the Phase 1/2 study, which includes three parts: a Phase 1 dose escalation, a part 1 (Phase 1) expansion and a Phase 2 expansion. In the study, 281 patients had relapsed or refractory acute myeloid leukemia and 214 of the relapsed or refractory acute myeloid leukemiapatients were treated at 100 mg daily. Data reported include patients receiving enasidenib at total daily doses ranging from 50 mg to 650 mg in the dose-escalation arm and 100 mg daily in the Phase 1 and Phase 2 expansion arms. A maximum tolerated dose was not reached. The median age of the relapsed or refractory acute myeloid leukemiapatients enrolled in the study is 68 (ranging from 19-100). Patients with relapsed or refractory acute myeloid leukemia received a median of two prior lines of therapy (ranging from one to 14).
• The overall safety profile observed for enasidenib was consistent with previously reported data. The most common treatment-emergent adverse events were nausea (48%), diarrhea (41%), fatigue (41%), decreased appetite (34%) and blood bilirubin increased (33%). For all patients in the study, 26.1 percent had treatment-related serious adverse events (SAEs), notably IDH differentiation syndrome (7%), leukocytosis (4%), tumor lysis syndrome (3%) and hyperbilirubinemia (2%).
• Data from 214 of the relapsed or refractory acute myeloid leukemia patients with an IDH2 mutation who were treated at the recommended Phase 2 starting dose of 100 mg daily demonstrated a 37 percent (79 of 214 patients) overall response rate, which was the primary endpoint of the study. Further, the complete response rate was 20.1 percent (43 of 214 patients).
• Median duration of response was 5.6 months [95% CI 4.6, 7.4] for all patients who responded and 8.8 months [95% CI 5.6, NR] for patients who achieved a CR. Median time to first response was 1.9 months (0.5-11.1) and median time to complete response was 3.7 months (0.7-11.2). At the time of the data cut-off, median overall survival (OS) as observed in the study was 8.3 months [95% CI 7.5,9.4]. Additional results including qualitative improvement in response over time, improvement in hematological parameters over time, overall survival for patients achieving a complete response  and transfusion independence were also reported.
• Enasidenib continues to be studied in the following ongoing clinical trials:
• - the phase III IDHENTIFY study is evaluating the efficacy and safety of enasidenib versus conventional care regimens in older patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation (NCT02577406)
• - a phase 1b study of either enasidenib or ivosidenib in combination with standard induction and consolidation chemotherapy in newly diagnosed AML (NCT02632708) - a phase 1/2 study of either enasidenib or ivosidenib in combination with azacitidine in newly diagnosed AML (NCT02677922)

   

Is general: Yes