Next-generation HMAs and inhibitors of other posttranscriptional/posttranslational marks
| Agents . | Mechanism of action . | Phase of development . | Comments . | Reference . |
|---|---|---|---|---|
| ASTX727 | DNMT inhibition | Phase 1/2 | Intermediate 2/high-risk MDS-HMA failure in phase 1, HMA-naive in phase 2 | NCT02103478 |
| Guadecitabine (SGI-110) | DNMT inhibition | Phase 3 | Intermediate 2/high-risk MDS-HMA failure | NCT02907359 |
| Pracinostat azacitidine | HDAC inhibition DNMT inhibition | Phase 2 | MDS-HMA naive; high or very high-risk; stage 1, open label; stage 2, randomized, placebo controlled | NCT03151304 |
| CPI-0610 | BET inhibition | Phase 1 | MDS excludes low or very low-risk disease, MDS/MPN, AML, myelofibrosis | NCT02158858 |
| RO6870810/TEN-010 | BET inhibition | Phase 1 | MDS-HMA failure, AML-R/R | NCT02308761 |
| GSK2879552* | LSD1 inhibition | Phase 2 | MDS-HMA failure; single-agent cohort or combination with azacitidine cohort | NCT02929498 |
| Tranylcypromine | LSD1 inhibition | Phase 1 | +ATRA in MDS-R/R and AML-R/R | NCT02273102 |
| Phase 1/2 | +ATRA and L-DAC in MDS-HMA failure and AML-R/R | NCT02717884 | ||
| Pevonedistat azacitidine† | NAE inhibition | Phase 2 | MDS or CMML HMA naive with high or very high-risk and/or excess blasts | NCT02610777 |
| DNMT inhibition | Randomized, open label |
| Agents . | Mechanism of action . | Phase of development . | Comments . | Reference . |
|---|---|---|---|---|
| ASTX727 | DNMT inhibition | Phase 1/2 | Intermediate 2/high-risk MDS-HMA failure in phase 1, HMA-naive in phase 2 | NCT02103478 |
| Guadecitabine (SGI-110) | DNMT inhibition | Phase 3 | Intermediate 2/high-risk MDS-HMA failure | NCT02907359 |
| Pracinostat azacitidine | HDAC inhibition DNMT inhibition | Phase 2 | MDS-HMA naive; high or very high-risk; stage 1, open label; stage 2, randomized, placebo controlled | NCT03151304 |
| CPI-0610 | BET inhibition | Phase 1 | MDS excludes low or very low-risk disease, MDS/MPN, AML, myelofibrosis | NCT02158858 |
| RO6870810/TEN-010 | BET inhibition | Phase 1 | MDS-HMA failure, AML-R/R | NCT02308761 |
| GSK2879552* | LSD1 inhibition | Phase 2 | MDS-HMA failure; single-agent cohort or combination with azacitidine cohort | NCT02929498 |
| Tranylcypromine | LSD1 inhibition | Phase 1 | +ATRA in MDS-R/R and AML-R/R | NCT02273102 |
| Phase 1/2 | +ATRA and L-DAC in MDS-HMA failure and AML-R/R | NCT02717884 | ||
| Pevonedistat azacitidine† | NAE inhibition | Phase 2 | MDS or CMML HMA naive with high or very high-risk and/or excess blasts | NCT02610777 |
| DNMT inhibition | Randomized, open label |
L-DAC, low-dose cytarabine; R/R, relapsed and/or refractory.
*Not yet recruiting at time of manuscript submission.
†Accrual is complete.