Table 2.
Clinical trials with IDH-targeted therapies in gliomas with available data.
| Reference | NCT Number | Study Design | Treatment | Population | Main Results | Adverse Events (in ≥10% of Patients) |
|---|---|---|---|---|---|---|
| Mellinghoff, I.K. et al., 2020 [40] | NCT02073994 | Phase I | Ivosidenib (AG-120) single agent | Advanced IDH1-mut solid tumors 35 non-enhancing recurrent gliomas 31 enhancing recurrent gliomas |
500 mg once daily selected for expansion part DCR 88% vs. 45%; median PFS 13.6 vs. 1.4 months in non-enhancing vs. enhancing cohort |
No DLT Headache; fatigue; nausea; vomiting; seizure; diarrhea; aphasia; hyperglycemia; neutropenia; depression; hypophosphatemia; paresthesia |
| Mellinghoff, I.K. et al., 2021 [41] | NCT02481154 | Phase I | Vorasidenib (AG-188) single agent | Advanced IDH1 and/or IDH2-mut solid tumors 22 non-enhancing recurrent gliomas 30 enhancing recurrent gliomas |
Recommended dose <100 mg in gliomas Non-enhancing glioma: ORR 18% (1 PR; 3 minor responses; 17 SD) Enhancing glioma: ORR 0% (17 SD) Median PFS: 36.8 vs. 3.6 months in non-enhancing vs. enhancing groups |
DLT (grade ≥2 ALT/AST increase) in 5 pts at ≥100 mg dose levels Headache; AST/ALT increase; fatigue; nausea; seizure; hyperglicemia; vomiting; constipation; dizziness; neutropenia; cough; diarrhea; aphasia; hypoglycemia |
| Mellinghoff, I.K. et al., 2019 [42] | NCT03343197 | Phase I | Perioperative Ivosidenib (AG-120) (n = 13) or vorasidenib (AG-188) (n = 14) single agent | Recurrent non-enhancing IDH1R132H-mut LGGs undergoing craniotomy | 2-HG concentration 92% (ivosidenib) and 92.5% (vorasidenib) lower in resected tumor tissue of treated patients | Diarrhea; constipation; hypocalcemia; nausea; anemia; hyperglicemia; pruritus; headache; fatigue |
| Wick, A. et al., 2021 [43] | NCT02746081 | Phase I | BAY-1436032 single agent | Advanced IDH1R132X-mut solid tumors 26 LGG astrocytoma 13 LGG oligodendroglioma 16 GBM |
1500 mg twice daily selected for expansion cohorts LGG: ORR 11% (1 CR; 3 PR; 15 SD) GBM: ORR 0%, SD 29%. PFS-rate at three months: 0.31 vs. 0.22 in LGG vs. GBM |
No DLT Fatigue; disgeusia |
| Natsume, A. et al., 2019 [44] | NCT03030066 | Phase I | DS-100b single agent | Recurrent/progressive IDH1R132X-mut glioma | 125–1400 mg twice daily Non-enhancing glioma (n = 9): 2 minor responses; 7 SD Enhancing glioma (n = 29): 1 CR; 3 PR; 10 SD |
DLT (grade 3 WBC decrease) at 1000 mg twice daily Skin hyperpigmentation; diarrhea; pruritus; nausea; rash; headache |
| Platten, M. et al., 2021 [45] | NCT02454634 | Phase I | IDH1-vac single agent | Newly diagnosed IDHR132H-mut grade 3 or 4 astrocytomas | 93.3% IDH1-vac induced immune response 3-years PFS: 63% 3-years OS: 84% |
No RLTs Mild site reactions |
2-HG 2-Hydroxyglutarate; ALT alanine transaminase; AST aspartate transaminase; CR complete response; DCR disease control rate; DLT dose-limiting toxicity; GBM glioblastoma; IDH Isocitrate dehydrogenase; LGG low-grade glioma; ORR objective response rate; OS overall survival; PFS progression-free survival; PR partial response; RLT regime-limiting toxicity; SD stable disease; WBC white blood cells.