Combination strategies involving epigenetic therapies currently in clinical trials
| Drug . | Targets . | Phase . | Date . | Clinical trial . |
|---|---|---|---|---|
| Combinations of epigenetic therapies | ||||
| Azacitidine + entinostat (MS275) | DNMT + HDAC | 2 | 2011 | NCT01305499 |
| Azacitidine + FT-2102 | DNMT1 + IDH1 | 1/2 | 2016 | NCT02719574 |
| Azacitidine + LSD1 inhibitor (NCB059872) | DNMT1 + LSD1 | 1/2 | 2016 | NCT02712905 |
| Azacitidine + ivosidenib (AG-120) | DNMT + IDH1 | 3 | 2017 | NCT03173248 |
| Azacitidine + pracinostat (SB939) | DNMT + HDAC | 3 | 2017 | NCT03151408 |
| Decitabine + vorinostat before or during FLAG | DNMT + HDAC | 1 | 2017 | NCT03263936 |
| Azacitidine + PRMT5 inhibitor (GSK3326595) | DNMT + PRMT5 | 1 | 2018 | NCT03614728 |
| Low-dose azacitidine + vorinostat after alloHSCT | DNMT + HDAC | 1 | 2019 | NCT03843528 |
| Epigenetic therapies in combination with immunotherapies | ||||
| Azacitidine + nivolumab (MDX-1106) +/or ipilimumab (MDX-010) | DNMT + PD-1 + CTLA-4 | 2 | 2015 | NCT02397720 |
| Azacitidine + pembrolizumab (MK-3475) | DNMT + PD-1 | 2 | 2016 | NCT02845297 |
| Decitabine + ipilimumab (MDX-010) | DNMT + CTLA-4 | 1 | 2016 | NCT02890329 |
| Guadecitabine + atezolizumab (MPDL 3280A) | DNMT + PD-L1 | 1/2 | 2016 | NCT02935361 |
| Decitabine + PDR001 +/or MBG453 | DNMT + PD-1 + TIM-3 | 1 | 2017 | NCT03066648 |
| Azacitidine + Hu5F9-G4 | DNMT + CD47 | 1 | 2017 | NCT03248479 |
| Decitabine + CDX-1401 + poly ICLC + nivolumab (MDX-1106) | DNMT + DEC-205 + TLR-3 + PD-1 | 1 | 2017 | NCT03358719 |
| Decitabine + avelumab | DNMT + PD-L1 | 1 | 2018 | NCT03395873 |
| Azacitidine + nivolumab (ADVL1412) | DNMT + PD-1 | 1/2 | 2019 | NCT03825367 |
| Epigenetic therapies in combination with targeted therapies | ||||
| Azacitidine + milademetan | DNMT + MDM2 | 1 | 2014 | NCT02319369 |
| Decitabine + rapamycin or ribavirin | DNMT + mTOR | 1/2 | 2014 | NCT02109744 |
| Decitabine + BI836858 | DNMT + CD33 | 2 | 2015 | NCT02632721 |
| Decitabine + BP1001 | DNMT + Grb-2 | 2 | 2016 | NCT02781883 |
| Azacitidine + gilteritinib (ASP2215) | DNMT + FLT3 | 2/3 | 2016 | NCT02752035 |
| Decitabine + talazoparib | DNMT + PARP | 1/2 | 2016 | NCT02878785 |
| Decitabine + onvansertib | DNMT + PLK1 | 1b/2 | 2017 | NCT03303339 |
| Azacitidine + AZD2811 nanoparticles | DNMT + AURKB | 2 | 2017 | NCT03217838 |
| Azacitidine + SL-401 | DNMT + IL3 | 1 | 2017 | NCT03113643 |
| Decitabine + AMG-232 | DNMT + MDM2 | 1 | 2017 | NCT03041688 |
| Decitabine + pevonedistat (MLN4924) | DNMT + NEDD8 | 1 | 2017 | NCT03009240 |
| Azacitidine + pevonedistat | DNMT + NEDD8 | 3 | 2017 | NCT03268954 |
| Decitabine + venetoclax (ABT-199) | DNMT + BCL-2 | 2 | 2018 | NCT03404193 |
| Azacitidine + pevonedistat | DNMT + NEDD8 | 2 | 2018 | NCT03709576 |
| Azacitidine + HMPL-523 | DNMT + SYK | 1 | 2018 | NCT03483948 |
| Decitabine + quizartanib (AC-220) | DNMT + FLT3 | 1/2 | 2018 | NCT03661307 |
| Azacitidine + enasidenib mesylate (AG-221 mesylate) | DNMT + IDH2 | 2 | 2018 | NCT03683433 |
| Azacitidine + nintedanib (BIBF-1120) | DNMT + VEGF + FGFR + PDGFR | 1 | 2018 | NCT03513484 |
| Belinostat (PCD-101) + pevonedistat (MLN4924) | HDAC + NEDD8 | 1 | 2018 | NCT03772925 |
| Azacitidine + glasdegib (PF-04449913) | DNMT + SHH | 3 | 2018 | NCT03416179 |
| Pracinostat + gemtuzumab ozogamicin | HDAC + CD33 | 1 | 2019 | NCT03848754 |
| Azacitidine or decitabine + venetoclax (ABT-199) | DNMT + BCL-2 | 3 | 2019 | NCT03941964 |
| Azacitidine + APR-246 | DNMT + P53 | 2 | 2019 | NCT03931291 |
| Drug . | Targets . | Phase . | Date . | Clinical trial . |
|---|---|---|---|---|
| Combinations of epigenetic therapies | ||||
| Azacitidine + entinostat (MS275) | DNMT + HDAC | 2 | 2011 | NCT01305499 |
| Azacitidine + FT-2102 | DNMT1 + IDH1 | 1/2 | 2016 | NCT02719574 |
| Azacitidine + LSD1 inhibitor (NCB059872) | DNMT1 + LSD1 | 1/2 | 2016 | NCT02712905 |
| Azacitidine + ivosidenib (AG-120) | DNMT + IDH1 | 3 | 2017 | NCT03173248 |
| Azacitidine + pracinostat (SB939) | DNMT + HDAC | 3 | 2017 | NCT03151408 |
| Decitabine + vorinostat before or during FLAG | DNMT + HDAC | 1 | 2017 | NCT03263936 |
| Azacitidine + PRMT5 inhibitor (GSK3326595) | DNMT + PRMT5 | 1 | 2018 | NCT03614728 |
| Low-dose azacitidine + vorinostat after alloHSCT | DNMT + HDAC | 1 | 2019 | NCT03843528 |
| Epigenetic therapies in combination with immunotherapies | ||||
| Azacitidine + nivolumab (MDX-1106) +/or ipilimumab (MDX-010) | DNMT + PD-1 + CTLA-4 | 2 | 2015 | NCT02397720 |
| Azacitidine + pembrolizumab (MK-3475) | DNMT + PD-1 | 2 | 2016 | NCT02845297 |
| Decitabine + ipilimumab (MDX-010) | DNMT + CTLA-4 | 1 | 2016 | NCT02890329 |
| Guadecitabine + atezolizumab (MPDL 3280A) | DNMT + PD-L1 | 1/2 | 2016 | NCT02935361 |
| Decitabine + PDR001 +/or MBG453 | DNMT + PD-1 + TIM-3 | 1 | 2017 | NCT03066648 |
| Azacitidine + Hu5F9-G4 | DNMT + CD47 | 1 | 2017 | NCT03248479 |
| Decitabine + CDX-1401 + poly ICLC + nivolumab (MDX-1106) | DNMT + DEC-205 + TLR-3 + PD-1 | 1 | 2017 | NCT03358719 |
| Decitabine + avelumab | DNMT + PD-L1 | 1 | 2018 | NCT03395873 |
| Azacitidine + nivolumab (ADVL1412) | DNMT + PD-1 | 1/2 | 2019 | NCT03825367 |
| Epigenetic therapies in combination with targeted therapies | ||||
| Azacitidine + milademetan | DNMT + MDM2 | 1 | 2014 | NCT02319369 |
| Decitabine + rapamycin or ribavirin | DNMT + mTOR | 1/2 | 2014 | NCT02109744 |
| Decitabine + BI836858 | DNMT + CD33 | 2 | 2015 | NCT02632721 |
| Decitabine + BP1001 | DNMT + Grb-2 | 2 | 2016 | NCT02781883 |
| Azacitidine + gilteritinib (ASP2215) | DNMT + FLT3 | 2/3 | 2016 | NCT02752035 |
| Decitabine + talazoparib | DNMT + PARP | 1/2 | 2016 | NCT02878785 |
| Decitabine + onvansertib | DNMT + PLK1 | 1b/2 | 2017 | NCT03303339 |
| Azacitidine + AZD2811 nanoparticles | DNMT + AURKB | 2 | 2017 | NCT03217838 |
| Azacitidine + SL-401 | DNMT + IL3 | 1 | 2017 | NCT03113643 |
| Decitabine + AMG-232 | DNMT + MDM2 | 1 | 2017 | NCT03041688 |
| Decitabine + pevonedistat (MLN4924) | DNMT + NEDD8 | 1 | 2017 | NCT03009240 |
| Azacitidine + pevonedistat | DNMT + NEDD8 | 3 | 2017 | NCT03268954 |
| Decitabine + venetoclax (ABT-199) | DNMT + BCL-2 | 2 | 2018 | NCT03404193 |
| Azacitidine + pevonedistat | DNMT + NEDD8 | 2 | 2018 | NCT03709576 |
| Azacitidine + HMPL-523 | DNMT + SYK | 1 | 2018 | NCT03483948 |
| Decitabine + quizartanib (AC-220) | DNMT + FLT3 | 1/2 | 2018 | NCT03661307 |
| Azacitidine + enasidenib mesylate (AG-221 mesylate) | DNMT + IDH2 | 2 | 2018 | NCT03683433 |
| Azacitidine + nintedanib (BIBF-1120) | DNMT + VEGF + FGFR + PDGFR | 1 | 2018 | NCT03513484 |
| Belinostat (PCD-101) + pevonedistat (MLN4924) | HDAC + NEDD8 | 1 | 2018 | NCT03772925 |
| Azacitidine + glasdegib (PF-04449913) | DNMT + SHH | 3 | 2018 | NCT03416179 |
| Pracinostat + gemtuzumab ozogamicin | HDAC + CD33 | 1 | 2019 | NCT03848754 |
| Azacitidine or decitabine + venetoclax (ABT-199) | DNMT + BCL-2 | 3 | 2019 | NCT03941964 |
| Azacitidine + APR-246 | DNMT + P53 | 2 | 2019 | NCT03931291 |
A list of currently active clinical trials that involve epigenetic therapies in combination with targeted therapies, immunotherapies, and/or other epigenetic therapies for the treatment of AML.
alloHSCT, allogeneic hematopoietic stem cell transplantation; AURKB, Aurora kinase B; BCL-2, B-cell lymphoma 2; DNMT, DNA methyltransferase; FGFR, fibroblast growth factor receptor; Grb2, growth factor receptor bound protein 2; HDAC, histone deacetylase; IDH, isocitrate dehydrogenase; IL3, interleukin 3; LSD1, lysine-specific histone demethylase 1; MDM2, mouse double minute 2; mTOR, mammalian target of rapamycin; PARP, poly ADP ribose polymerase; PD-1, programmed cell death protein 1; PDGFR, platelet-derived growth factor receptor; PD-L1, programmed cell death ligand 1; PLK1, polo-like kinase 1; PRMT5, protein arginine N-methyltransferase 5; Shh, Sonic hedgehog; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; TLR-3, Toll-like receptor 3; VEGF, vascular endothelial growth factor.