Table 1.
2-HG-targeted therapies.
| Agent | Target | FDA-approved indications | Trial | Phase | Participants | Enrollment | Status | Reference |
|---|---|---|---|---|---|---|---|---|
| FDA-approved agents | ||||||||
| Ivosidenib (AG-120) | mIDH1 | mIDH1 AML in patients ≥75 years old or not suitable for intensive chemotherapy Adult patients with relapsed or refractory mIDH1 myelodysplastic syndromes (MDS) |
NCT02074839 | 1 | Advanced hematologic malignancies with an IDH1 mutation | 291 (estimated) | Recruiting | [156] |
| In combination with azacitidine for mIDH1 AML in patients ≥75 years old or not suitable for chemotherapy | NCT03173248 | 3 | Previously intreated AML with an IDH1 mutation | 146 | Active, not recruiting | [157] | ||
| Adult patients with previously treated, locally advanced, or metastatic mIDH1 cholangiocarcinoma | NCT02989857 | 3 | Previously treated nonresectable or metastatic cholangiocarcinoma with an IDH1 Mutation | 187 | Completed | [158] | ||
| Enasidenib (AG-221) | mIDH2 | Adult patients with relapsed or refractory mIDH2 AML | NCT01915498 | 1/2 | Advanced hematologic malignancies with an IDH2 mutation | 345 | Active, not recruiting | [159] |
| Olutasidenib (FT-2102) | mIDH1 | Adult patients with relapsed or refractory mIDH1 AML | NCT02719574 | 1/2 | AML or MDS with an IDH1 mutation | 336 | Active, not recruiting | [160] |
| Agents not yet approved by the FDA | ||||||||
| Vorasidenib (AG-881) | mIDH1/2 | / | NCT04164901 | 3 | Residual or recurrent grade 2 glioma with an IDH1/2 mutation who have undergone surgery as their only treatment | 331 | Active, not recruiting | [161] |
| NCT03343197 | 1 | Recurrent, non-enhancing, IDH1 mutant, low-grade glioma for patients who require surgery | 49 | Active, not recruiting | [162] | |||
| Safusidenib (AB-218) | mIDH1 | / | NCT05577416 | 0 | mIDH1 low-grade glioma who have not received prior radiation or chemotherapy and are planned to undergo surgical resection | 10 (estimated) | Recruiting | / |
| NCT05814536 | 1 | Advanced mIDH1 cholangiocarcinoma and other solid tumors who have failed at least one prior therapy in the advanced stage | 63 (estimated) | Recruiting | / | |||
| NCT05303519 | 2 | Recurrent or progressive histologically confirmed mIDH1 WHO grade 2/3 glioma | 95 (estimated) | Recruiting | / | |||
| IDH305 | mIDH1 | / | NCT02381886 | 1 | Advanced malignancies that harbor IDH1R132 mutations | 166 | Active, not recruiting | [163] |
| LY3410738 | mIDH1/2 | / | NCT04603001 | 1 | Advanced hematologic malignancies with IDH1 or IDH2 mutations | 260 (estimated) | Active, not recruiting | / |
| BAY1436032 | mIDH1 | / | NCT03127735 | 1 | mIDH1R132X advanced AML | 27 | Completed | [164] |
| NCT02746081 | 1 | mIDH1R132X advanced solid tumors | 81 | Active, not recruiting | [165] | |||