Table 3.
Investigational agents in clinical development for AML and/or MDS
| Class/Pathway | Investigational agent | Alternative names | Proposed MOA/Target | AML/MDS trials |
|---|---|---|---|---|
| FLT3 inhibitor | Quizartinib | Type I FLT3 inhibitor | NCT04107727, NCT03135054, NCT04493138, NCT04128748, NCT03735875, NCT02668653, NCT01892371, NCT03661307, NCT03793478, NCT04047641, NCT04687761, NCT04112589, NCT02984995, NCT03723681, NCT02039726, NCT02834390, NCT01565668, NCT02675478, NCT00462761, NCT01468467, NCT01390337, NCT00989261, NCT01411267 | |
| Crenolanib | Type I FLT3 inhibitor | NCT03258931, NCT02400255, NCT03250338, NCT01657682, NCT01522469, NCT02400281, NCT02626338, NCT02283177, NCT02270788 | ||
| Ponatinib | Type I FLT3 inhibitor | NCT02428543, NCT03690115 | ||
| Luxeptinib | CG-806 | Type I FLT3 inhibitor | NCT04477291 | |
| HM43239 | Type I FLT3 inhibitor | NCT03850574 | ||
| FF-10101 | Type I FLT3 inhibitor | NCT03194685, NCT02193958 | ||
| IDH inhibitor | LY3410738 | IDH1/2 inhibitor | NCT04603001 | |
| BCL2/MCL1 | S65487 | VOB560 | BCL2 inhibitor | NCT04742101, NCT03755154, NCT04702425 |
| S55746 | BCL201 | BCL2 inhibitor | NCT02920541 | |
| AMG 176 | MCL1 inhibitor | NCT05209152, NCT02675452 | ||
| AZD5991 | MCL1 inhibitor | NCT03013998 | ||
| S64315 | MIK665 | MCL1 inhibitor | NCT04629443, NCT03672695, NCT02979366, NCT02992483, NCT04702425 | |
| Mutant P53 | Eprenetapopt | APR-246 | Mutant p53 reactivation, cellular redox modification, ferroptosis | NCT03931291, NCT04214860, NCT03745716, NCT03072043, |
| Epigenetic pathways | Ziftomenib | KO-539 | Menin-MLL inhibitor | NCT04067336 |
| Revumenib | SNDX-5613, VTP50469 | Menin inhibitor | NCT05406817, NCT05326516, NCT04065399, NCT05360160, NCT03013998 | |
| Pinometostat | EPZ5676 | DOT1L inhibitor | NCT03701295 | |
| Iadademstat | ORY-1001 | KDM1A inhibitor | NCT05546580 | |
| Entinostat | SYNDX-275, MS-275 | HDAC1/3 inhibitor | NCT00101179, NCT00313586, NCT00462605, NCT00015925, NCT02936752 | |
| Other oncogenic pathways | Pevonedistat | TAK-924, MLN4924 | NEDD8 activator | NCT03459859, NCT03772925, NCT04266795, NCT03813147, NCT03268954 |
| Entospletinib | GS-9973 | Syk inhibitor | NCT05020665, NCT03013998 | |
| Olaparib | PARP inhibitor | NCT03953898 | ||
| Milademetan | DS-3032, RAIN-32 | MDM2/HDM2 inhibitor | NCT03671564, NCT03634228 | |
| Siremadlin | HDM201 | MDM2/HDM2 inhibitor | NCT05447663, NCT05155709 | |
| Uproleselan | GMI-1271 | E-selectin antagonist | NCT04964505, NCT05569512, NCT05054543, NCT04839341, NCT04848974, NCT03616470, NCT02306291 | |
| Tamibarotene | SY-1425 | Retinoic acid receptor alpha agonist | NCT04797780, NCT04905407, NCT02807558 | |
| JNJ-74856665 | Dihydroorotate dehydrogenase inhibitor | NCT04609826 | ||
| PRT543 | PRMT5 inhibitor | NCT03886831 | ||
| H3B-8800 | RVT-2001 | Splicing modulator | NCT0281540 | |
| Emavusertib | CA-4948 | IRAK4 inhibitor | NCT04278768, NCT05178342 | |
| Targeted Immune inhibitors | Magrolimab | Hu5F9-G4, ONO-7913 | Anti-CD47 | NCT04313881, NCT05367401, NCT05079230, NCT04435691, NCT03248479, NCT04778397, NCT04778410, NCT02678338 |
| Lemzoparlimab | TJ011133, TJC4 | Anti-CD47 | NCT04202003, NCT04912063 | |
| Ipilimumab | Anti-CTLA4 | NCT01757639, NCT02890329, NCT03600155, NCT02397720, NCT03912064, NCT02846376, NCT00060372, NCT01822509, NCT02530463 | ||
| Nivolumab | Anti-PD-1 | NCT03417154, NCT02530463, NCT02464657, NCT03600155, NCT03358719, NCT03092674, NCT02846376, NCT02532231, NCT02397720, NCT01822509, NCT04913922, NCT03825367, NCT02275533, NCT04277442 | ||
| Pembrolizumab | Anti-PD-1 | NCT02996474, NCT02845297, NCT02708641, NCT03769532, NCT02768792, NCT02771197, NCT04284787, NCT04214249, NCT03969446, NCT04372706, NCT03761914, NCT03144245, NCT02981914, NCT03094637, NCT02936752, NCT01953692 | ||
| Spartalizumab | PDR001 | Anti-PD-1 | NCT03066648 | |
| Relatlimab | Anti-LAG3 | NCT04913922 | ||
| Sabatolimab | MBG453 | Anti-TIM3 | NCT04812548, NCT04623216, NCT04878432, NCT05367401, NCT05201066, NCT04150029, NCT03946670, NCT04266301 | |
| Decoy receptor | Evorpacept | ALX148 | Anti-CD47 | NCT04755244, NCT04417517 |
| ADC | IMGN632 | Anti-CD123 | NCT03386513, NCT04086264, NCT05320380 | |
| Cusatuzumab | ARGX-110 | Anti-CD70 | NCT04023526, NCT04241549, NCT04150887, NCT03030612 | |
| Vadastuximab | SGN-CD33A | Anti-CD33 | NCT02326584, NCT01902329 | |
| BITE/DART | AMV564 | CD33 x CD3 | NCT03144245, NCT03516591 | |
| AMG 427 | FLT3 x CD3 | NCT03541369 | ||
| Flotetuzumab | MGD006 | CD123 x CD3 | NCT05506956, NCT04158739, NCT04582864, NCT04681105 | |
| Vibecotamab | XmAB14045 | CD123 x CD3 | NCT02730312, NCT05285813 | |
| APVO436 | CD123 x CD3 | NCT03647800 |
A summary of agents without FDA approval or NCCN recommendation for the treatment of AML/MDS but under investigation for the treatment of AML and/or MDS is shown along with proposed mechanisms of action and clinical trials that are not yet recruiting, recruiting, enrolling, active but not recruiting, or completed. Terminated or suspended studies have been omitted. Cellular therapies (i.e., CAR T cells) are not shown. MOA Mechanism of action, AML Acute myeloid leukemia, MDS Myelodysplastic syndrome, ADC Antibody–drug conjugate, BITE Bispecific T-cell engager, DART Dual affinity retargeting protein