Table 3.
The combination therapy of IDH1 inhibitors and other targeted drugs.
| IDH1 inhibitor | Combined drug | NCT No. | Condition | Conclusion/objective |
|---|---|---|---|---|
| Ivosidenib (AG-120) | Azacytidine (DNMT1 inhibitor) | NCT03173248 (Phase III) | AML | Recovery of blood counts; rates of febrile neutropenia and infections were reduced |
| Ivosidenib (AG-120) | Azacytidine (DNMT1 inhibitor) | NCT03503409 (Phase II) | AML; Myelodysplasia |
Evaluate the efficacy and safety in patient with IDH1 mutation-positive myelodysplastic syndrome |
| Ivosidenib (AG-120) | Nivolumab (anti-PD-1) | NCT04056910 (Phase II) | Metastatic cancer; Glioma |
Evaluate response to treatment, survival and safety events |
| Ivosidenib (AG-120) | Nivolumab (anti-PD-1) | NCT04044209 (Phase II) | AML; Myelodysplasia |
Evaluate safety and efficacy |
| Ivosidenib (AG-120) | Enasidenib (IDH2 inhibitor) | NCT02632708 (Phase I) | AML | Decrease in plasma and bone marrow 2-HG concentrations; CCR: 18.4% |
| Ivosidenib (AG-120) | Enasidenib (IDH2 inhibitor) | NCT03839771 (Phase III) | AML; Myelodysplasia |
Evaluate safety and efficacy |
| Ivosidenib (AG-120) | Enasidenib (IDH2 inhibitor) | NCT02677922 (Phase I/II) | AML | Treatment-emergent adverse events (TEAEs) including nausea, anemia and thrombocytopenia were reported |
| Ivosidenib (AG-120) | Vorasidenib (AG-881) | NCT03343197 (Phase I) | Glioma | Activation of IFN signaling and increased T-cell infiltration was observed |
| Ivosidenib (AG-120) | Venetoclax (Bcl-2 inhibitor) | NCT03471260 (Phase I/II) | AML; Hematologic cancer; Myelodysplasia; Myeloproliferative diseases |
Evaluate the safety and efficacy |
| Ivosidenib (AG-120) | Itraconazole (Hedgehog inhibitor) | NCT02831972 (Phase I) | Healthy volunteers | Ivosidenib alone or with itraconazole were well-tolerated with similar favorable safety profiles |
| Ivosidenib (AG-120) | Enasidenib (IDH2 inhibitor) Fedratinib (JAK2 inhibitor) |
NCT04955938 (Phase 1b) | Chronic myeloid leukemia; Myelodysplasia; Myelofibrosis; Polycythemia vera; Thrombocythemia |
Evaluate the safety and efficacy |
| Ivosidenib (AG-120) | Azacytidine (DNMT1 inhibitor) Venetoclax (Bcl-2 Inhibitor) |
NCI-2018-00921 (Phase I/II) | Myeloid leukemia | One-year overall survival were 75%, 50% and 100% in newly diagnosed AML, relapsed/refractory (R/R) AML and myelodysplatic syndrome, CRR: 67% |
| Ivosidenib (AG-120) | Enasidenib (IDH2 inhibitor) Azacytidine (DNMT1 inhibitor) |
NCT02677922 (Phase I/II) | AML; Myelodysplasia; Myeloproliferative diseases |
ORR: 78% |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | NCT02677922 (Phase I/II) | AML | TRAE: 44% |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | NCT03683433 (Phase II) | AML | TEAE: 85% |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | NCT03383575 (Phase II) | AML | All patients reported leukocytosis. |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | AG221-AML-005 (Phase I/II) | AML | mOS remained unchanged (22.0 months) |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | NCT03013998 (Phase II) | AML | Low early death rate; High CR/CRi: 47%; yielded durable remissions |
| Enasidenib (AG-221) | Azacytidine (DNMT1 inhibitor) | NCT03683433 (Phase II) | AML; Chronic myelomonocytic leukemia; Myelodysplasia |
Evaluate the clinical activity of enasidenib in combination with azacitidine for patients with relapsed/refractory acute myeloid leukemia |
| Enasidenib (AG-221) | Cobimetinib (MEK1 inhibitor) | NCT05441514 (Phase Ib) | AML | Evaluate the efficacy and safety |
| Enasidenib (AG-221) | Venetoclax (Bcl-2 inhibitor) | 19-5939 (Phase I/II) | AML; Myelodysplasia; Myeloproliferative diseases |
Evaluate the safety, tolerability, efficacy, and best dose of venetoclax administered in combination with enasidenib in patients with blood cancers |
| Enasidenib (AG-221) | Daunorubicin (topoisomerase II) Cytarabine (DNA polymerase) |
NCT03825796 (Phase II) | AML | Evaluate the efficacy and safety |
| Enasidenib (AG-221) |
Azacytidine (DNMT1 inhibitor) Venetoclax (Bcl-2 inhibitor) |
NCT03683433 (Phase II) | AML | 6-month OS was 70%; CR/CRi: 100% (ND AML); CR/CRi: 58% (R/R AML) |
| Olutasidenib (FT-2102) | Cedazuridine (cytidine deaminase (CDA) inhibitor) Decitabine (deoxycytidine analog antimetabolite and a DNA methyltransferase inhibitor) |
NCT04013880 (Phase I/II) | AML; Myelodysplasia |
Evaluate the efficacy and safety |
| Olutasidenib (FT-2102) | Azacytidine (DNMT1 inhibitor) | NCT03684811 (Phase Ib/II) | Glioma | Dose-limiting toxicities ( ≥grade 3 transaminase elevations) were noted in combination group, meeting stopping criteria |
| Olutasidenib (FT-2102) | Azacytidine (DNMT1 inhibitor) | NCT02719574 (Phase I/II) | AML; Myelodysplasia |
mOS: 37.7 (monotherapy) versus 52.5 (combination therapy) weeks |
| Vorasidenib (AG-881) | Omeprazole (PPI) | NCT04128787 (Phase I) | Healthy volunteers | Evaluate the safety and tolerability |
| Vorasidenib (AG-881) | Lamotrigine (anticonvulsant agent) | NCT04015687 (Phase I) | Healthy volunteers | Evaluate the safety and pharmacokinetics |
| IDH1RpepvaccH (vaccine) | Avelumab (anti-PD-L1) | NCT03893903 (Phase I) | Glioma | Evaluate safety, tolerability and immunogenicity |
| IDH1RpepvaccH (vaccine) | Temozolomide (DNA alkylating) | NCT02454634 (Phase I) | Astrocytoma; Glioma; Oligodendroglioma |
TRAE: 90.6% |
| PEPIDH1M (vaccine) | Temozolomide (DNA alkylating) | NCT02193347 (Phase I) | Glioma | Evaluate the safety |
ND, new diagnosis; ORR, overall response rate; mOS, median overall survival; CRR, rate of complete remission; CR/Cri, complete remission/complete remission with incomplete recovery; TRAE, treatment related adverse events; TEAEs, treatment-emergent adverse events.