Table 2.
Ongoing clinical trials of IDH2 inhibitors in AML and myelodysplastic syndromes (MDS).
| Trial Identification (Sponsor) | Clinical Phase | Title | Disease and Objectives | Drugs | Status |
|---|---|---|---|---|---|
| NCT 01915498 (Agios) | Phase I, Phase II | Phase 1/2 study of AG-221 in subjects with advanced hematologic malignancies with an IDH2 mutation | Advanced AML Safety, tolerability, MTD |
AG-221 (Enasidenib) | Active, not recruiting |
| NCT 02577406 (Celgene) | Phase II | An efficacy and safety study of AG-221 (CC-90007) versus conventional care regimen in older subjects with late stage AML harboring an IDH2 mutation (IDHENTITY) | AML ≥60 years OS, ORR, EFS, duration of response, time to response |
Enasidenib, BSC, azacitidine, low-dose AraC, intermediate-dose AraC | Active, not recruiting |
| NCT 02632708 (Agios, Celgene) | Phase I | Safety study of AG-120 or AG-221 in combination with Induction and consolidation therapy in participants With newly diagnosed acute myeloid leukemia (AML) With an IDH1 and/or IDH2 mutation |
Newly diagnosed AML, AML arising from MDS, antecendent hematologic disorder or therapy Safety, tolerability, MTD |
Ivosidenib or enasidenib plus standard chemotherapy |
Active, not recruiting |
| NCT 02677922 (Celgene) | Phase I/Phase II | A safety and efficacy of oral AG-120 plus subcutaneous azacitidine and oral AG-221 plus subcutaneous azacitidine in subjects with newly diagnosed AML | AML DLT, Safety, Pharmacokinetics |
Ivosidenib or enasidenib plus azacytidine |
Active, not recruiting |
| NCT 03383575 (MD Anderson Cancer Center) | Phase II | Azacitidine and enasidenib in treating patients with IDH2-mutant myelodysplastic syndrome | High-risk MDS, R/R MDS Safety, ORR, EFS, OS |
Enasidenib plus azacitidine (arm 1, HNA-naive MDS), enosidenib (arm 2, R/R MDS) | Active, recruiting |
| NCT 03515512 (Massachusetts General Hospital) | Phase I | IDH2 inhibition using enasidenib as maintenance therapy for IDH2-mutant myeloid neoplasms following allogeneic stem cell transplantation | IDH2 mutant myeloid neoplasms |
Enasidenib | Active, recruiting |
| NCT 03683433 (MD Anderson Cancer Center) | Phase II | Enasidenib and zacitidine in treating patients with recurrent or refractory AML and IDH2 gene mutation | R/R AML ORR, EFS, OS |
Enasidenib plus azacitidine | Active, recruiting |
| NCT03728335 (City of Hope Medical Center) | Phase I | Enasidenib as maintenance therapy in treating patients with AML with IDH2 mutation after donor stem cell transplant | AML in post HCT Safety, tolerability, OS, EFS |
Enasidenib | Active, recruiting |
| NCT 03744390 (Groupe Francophone des Myelodysplasies) | Phase II | IDH2 (AG221) inhibitor in patients with IDH2 mutated myelodysplastic syndrome | High-risk, R/R MDS ORR, Duration of response |
Enasidenib | Active, recruiting |
| NCT 03825796 (Jonsson Comprehensive Cancer Center) | Phase II | CPX-351 and enasidenib in treating patients with released AML characterized by IDH2 mutation | Relapsed AML Remission rate, hematological toxicity |
Enasidenib plus CPX-351 (liposome-encapsulated daunorubicin-cytarabine) |
Active, recruiting |
| NCT 03839771 (Stichting Hemato-Oncologie voor Wolkvassenen, NL | Phase III | A study of ivosidenib or enasidenib in combination with induction therapy and consolidation therapy, followed by maintenance therapy in patients with newly diagnosed AML or myelodysplastic syndrome EB2, with an IND1 or IDH2 mutation, respectively, eligible for intensive chemotherapy (HOVON 150 AML) | IDH1 or IDH2 mutant AML or MDS EFS, OS, RFS |
Ivosidenib or enasidenib plus standard chemotherapy |
Active, recruiting |
| NCT 03881735 (Roswell Park Cancer Institute) | Phase II | Enasidenib in treating patients with relapsed or refractory AML with an IDH2 gene mutation | RR/AML EFS, OS |
Enasidenib after salvage chemotherapy | Active, recruiting |
| NCT 04203316 (Children’s Oncology Group) | Phase II | Enasidenib for the treatment of relapsed or refractory AML patients with an IDH2 mutation | Pediatric AML Safety, tolerability, pharmacokinetics |
Enasidenib | Active, recruiting |
Abbreviations: EFS: Event-free survival; OS: Overall survival; ORR: Overall response rate; CRR: Complete response rate; DLT: Dose limiting toxicity; MTD: Maximum tolerated dose; RFS: Relapse-free survival; PFS: Progression-free survival.