Table 2.
Targeted Therapies in Clinical Trial in Patients with IDH-mutant Glioma
| Mechanism of action | Therapy | Phase | Design | Tumor type | Trial |
|---|---|---|---|---|---|
| Treatment naive | |||||
| IDH inhibitor | Vorasidenib | III | • Randomized, placebo-controlled • Primary outcome: PFS |
• Non-enhancing tumors IDH-mutant glioma • Within 5 years of initial surgery • No prior RT or chemotherapy |
NCT04164901 |
| IDH inhibitor | DS-1001 | II | • Primary outcomes: ORR, incidence of TEAEs | • Treatment-naïve grade 2 IDH-mutant glioma | NCT04458272 |
| Glutaminase inhibitor | Telaglenastat + RT and TMZ | I | • Determine MTD and RP2D | • Grade 2 or 3 IDH-mutant glioma • No prior RT or TMZ |
NCT03528642 |
| CDK4/6 inhibitor | Palbociclib | II | • Non-randomized • Primary outcomes: PFS-6 |
• Grade 3 oligodendroglioma (newly diagnosed and recurrent) | NCT02530320 |
| Recurrent after treatment | |||||
| Demethylating agent | ASTX7272 (decitabine + cedazuridine) | 0/I | • Phase I dose escalation to determine MTD • Phase 0 surgical expansion for PD effects |
• Recurrent IDH-mutant glioma • Non-enhancing tumors |
NCT03922555 |
| Demethylating agent | 5-azacytidine | II | • Single arm • Primary outcome: PFS-6 |
• Recurrent grade 2 or 3 IDH-mutant glioma after standard treatment | NCT03666559 |
| PARP inhibitor | Niraparib | 0 | • Phase 0 to examine PK, PD and presence of chromosomal fusion | • Recurrent grade 2-4 IDH-mutant astrocytoma (Arm B only) | NCT05076513 |
| PARP inhibitor | Pamiparib + metronomic TMZ | I/II | • Alkylator resistant and not-alkylator resistant arms in Phase II • Surgical arm includes grade 4 tumors • Primary outcomes: MTD and radiologic response |
• Recurrent grade 2-4 IDH-mutant glioma | NCT03914742 |
| PPARP inhibitor | Olaparib + Durvalumab | II | • Non-randomized • Primary outcomes: ORR |
• Recurrent IDH-mutant glioma at first or second relapse (Cohort A) | NCT03991832 |
| CDK4/6 inhibitor | Palbociclib | II | • Non-randomized • Primary outcomes: PFS-6 |
• Grade 3 oligodendroglioma (newly diagnosed and recurrent) | NCT02530320 |
| CDK4/6 inhibitor | Abemaciclib | II | • Non-randomized, single arm • Primary outcomes: PFS-6 |
• Recurrent oligodendroglioma | NCT03220646 |
| DHODH inhibitor | BAY2402234 | 0 | • Phase 0 for PD effects | • Grade 4 recurrent IDH-mutant glioma | Pending |
| Immune checkpoint inhibitor + IDH inhibitor | Nivolumab + Ivosidenib | II | • Non-randomized, single arm • Primary outcomes: PFS-6, ORR |
• Recurrent IDH-mutant glioma • Enhancing disease |
NCT04056910 |