Other novel targeted agents and kinase inhibitors
| Agents . | Mechanism of action . | Phase of development . | Comments . | Reference . |
|---|---|---|---|---|
| Enasidenib (AG-221)* | IDH2 inhibition | Phase 1/2 | IDH2 mutant advanced and/or high-risk AML, MDS-RAEB1/2, or high-risk or R/R | NCT01915498 |
| Ivosidenib (AG-120)* | IDH1 inhibition | Phase 1/2 | IDH1 R132 mutant advanced heme malignancy | NCT02074839 |
| H3B8800 | Splicing modulator | Phase 1 | MDS-HMA failure/intolerant, intermediate-2 or high-risk; AML-R/R/U; CMML previously treated | NCT02841540 |
| Venetoclax azacitidine | BCL2 inhibition DNMT inhibition | Phase 1 | MDS- HMA failure, intermediate-2 or high-risk, single-agent venetoclax and azacitidine+venetoclax combination cohorts | NCT02966782 |
| Venetoclax azacitidine | BCL2 inhibition DNMT inhibition | Phase 2 | MDS- HMA naive, intermediate-2/high-risk and > 5% blasts, randomized | NCT02942290 |
| Rigosertib | Multitargeted kinase inhibition | Phase 3 | HMA failure MDS-EB, includes RAEB-t; phase 3 vs physician’s choice (includes best supportive care; azacitidine or DEC use also permitted) | NCT02562443 |
| Ibrutinib azacitidine | BTK inhibition DNMT inhibition | Phase 1b | Intermediate or higher-risk MDS, HMA failure (dose escalation stage only), HMA naive included in both stages of study | NCT02553941 |
| Selumetinib azacitidine† | MEK inhibition DNMT inhibition | Phase 1 | Advanced myeloid malignancies including MDS-relapsed/refractory |
| Agents . | Mechanism of action . | Phase of development . | Comments . | Reference . |
|---|---|---|---|---|
| Enasidenib (AG-221)* | IDH2 inhibition | Phase 1/2 | IDH2 mutant advanced and/or high-risk AML, MDS-RAEB1/2, or high-risk or R/R | NCT01915498 |
| Ivosidenib (AG-120)* | IDH1 inhibition | Phase 1/2 | IDH1 R132 mutant advanced heme malignancy | NCT02074839 |
| H3B8800 | Splicing modulator | Phase 1 | MDS-HMA failure/intolerant, intermediate-2 or high-risk; AML-R/R/U; CMML previously treated | NCT02841540 |
| Venetoclax azacitidine | BCL2 inhibition DNMT inhibition | Phase 1 | MDS- HMA failure, intermediate-2 or high-risk, single-agent venetoclax and azacitidine+venetoclax combination cohorts | NCT02966782 |
| Venetoclax azacitidine | BCL2 inhibition DNMT inhibition | Phase 2 | MDS- HMA naive, intermediate-2/high-risk and > 5% blasts, randomized | NCT02942290 |
| Rigosertib | Multitargeted kinase inhibition | Phase 3 | HMA failure MDS-EB, includes RAEB-t; phase 3 vs physician’s choice (includes best supportive care; azacitidine or DEC use also permitted) | NCT02562443 |
| Ibrutinib azacitidine | BTK inhibition DNMT inhibition | Phase 1b | Intermediate or higher-risk MDS, HMA failure (dose escalation stage only), HMA naive included in both stages of study | NCT02553941 |
| Selumetinib azacitidine† | MEK inhibition DNMT inhibition | Phase 1 | Advanced myeloid malignancies including MDS-relapsed/refractory |
BTK, Bruton tyrosine kinase; DEC, decitabine; MEK, mitogen-activated protein/extracellular signal-regulated kinase; RAEB, refractory anemia with excess blasts.
*No longer recruiting.
†Not yet recruiting, clinical trials.org listing pending at the time of manuscript submission,