Idhifa (enasidenib)

P1/2, N=84, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2025 --> Nov 2027

P1, N=4, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Oct 2026

Enasidenib plus venetoclax is safe, with no unexpected TEAEs or treatment-related deaths, and shows preliminary activity in patients with relapsed or refractory IDH2-mutated AML and MDS.

P2, N=1, Active, not recruiting, Children's Oncology Group | N=10 --> 1 | Trial completion date: Sep 2025 --> Oct 2026

Post-HCT enasidenib maintenance therapy was safe and well-tolerated, resulting in favorable relapse control and survival outcomes in AML patients carrying IDH2 mutations. Phase 2 multicenter study investigating effectiveness of enasidenib maintenance as a relapse-prevention strategy after allo-HCT is ongoing.

P2, N=10, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025

Selective inhibitors like ivosidenib (AG-120) and enasidenib (AG-221), targeting mutant IDH1 and IDH2 respectively, block 2- HG production and induce differentiation, achieving clinical success - particularly in AML...In response, novel approaches have emerged, such as covalent inhibitors like LY3410738, which irreversibly bind mutant residues, and dual inhibitors like vorasidenib (AG-881), which act on both IDH1 and IDH2 mutations and penetrate the blood-brain barrier for treating solid tumors...We underscore that discovering new antitumor compounds targeting IDH requires a collaborative effort across biomedical fields. These advancements aim to overcome resistance, broaden therapeutic options, and improve the effectiveness of IDH-targeted treatments.

P1, N=3, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting

P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2025 --> Sep 2027 | Trial primary completion date: Sep 2025 --> Sep 2027

In our practice, we continue to use 7 + 3 induction for fit patients, adding midostaurin or quizartinib for FLT3-mutated AML, or gemtuzumab ozogamicin for core binding factor (CBF) AML expressing CD33...In the presence of IDH1 mutations, we consider azacitidine combined with ivosidenib. If venetoclax is contraindicated or not tolerated, targeted therapies such as gilteritinib, ivosidenib, or enasidenib may be appropriate based on mutation profile...When feasible, clinical trial enrollment should be considered for newly diagnosed patients with these alterations. As the therapeutic landscape for AML continues to evolve, timely molecular characterization is more essential than ever to optimize outcomes and select the most appropriate frontline strategy.

P2, N=15, Recruiting, Washington University School of Medicine | Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Sep 2026 --> May 2027

Enasidenib was administered as a single agent in 18 patients, in combination with azacitidine in four patients, and with low-dose cytarabine in another one. Although enasidenib failed to demonstrate a clear overall survival advantage in phase 3 trials, the extended responses and long-term survivors observed herein underscore its therapeutic potential. Ultimately, our data support enasidenib's role as a targeted therapy for IDH2-mutated AML, indicating that expanded access to this agent is warranted to optimize outcomes in these challenging patient populations, especially for R/R AML patients.