Examples of molecularly targeted early phase and adaptive later stage trials where mutational information may inform therapeutics
| Therapeutic target . | Potentially sensitive genotypes . | Inhibitor . | Phase . | Trial identifier number . |
|---|---|---|---|---|
| Early phase | ||||
| Highly specific | ||||
| hDOT1L* | MLL rearranged | EPZ-5676 | I | NCT01684510 |
| IDH2 | IDH2 mutated | AG-221 | I | NCT019115498 |
| CDK6 | MLL rearranged | Palbociclib | Ib/IIa | NCT02310243† |
| Broader specificity | ||||
| BET proteins* | MLL rearranged, NPM1c, | OTX015 | I | NCT01713582 |
| other | GSK525762 | I | NCT01943851† | |
| XPO1/CRM-1 | NPM1c, other | KPT-330 (Selinexor) | I | NCT01607892 |
| BCL-2* | IDH2 mutated, other | venetoclax | II | NCT01994837 |
| Risk adapted later phase | ||||
| FLT3* | FLT3 mutated | Crenolanib | II | NCT01522469 |
| Quizartinib | II | NCT01236144 | ||
| Midostaurin | III | NCT00651261 | ||
| C-KIT* | C-KIT mutated | Dasatinib | III | NCT02013648 |
| CD33 | CBF leukemia | Gemtuzumab ozogamicin | III | ISRCTN17161961† |
| (Mylotarg) |
| Therapeutic target . | Potentially sensitive genotypes . | Inhibitor . | Phase . | Trial identifier number . |
|---|---|---|---|---|
| Early phase | ||||
| Highly specific | ||||
| hDOT1L* | MLL rearranged | EPZ-5676 | I | NCT01684510 |
| IDH2 | IDH2 mutated | AG-221 | I | NCT019115498 |
| CDK6 | MLL rearranged | Palbociclib | Ib/IIa | NCT02310243† |
| Broader specificity | ||||
| BET proteins* | MLL rearranged, NPM1c, | OTX015 | I | NCT01713582 |
| other | GSK525762 | I | NCT01943851† | |
| XPO1/CRM-1 | NPM1c, other | KPT-330 (Selinexor) | I | NCT01607892 |
| BCL-2* | IDH2 mutated, other | venetoclax | II | NCT01994837 |
| Risk adapted later phase | ||||
| FLT3* | FLT3 mutated | Crenolanib | II | NCT01522469 |
| Quizartinib | II | NCT01236144 | ||
| Midostaurin | III | NCT00651261 | ||
| C-KIT* | C-KIT mutated | Dasatinib | III | NCT02013648 |
| CD33 | CBF leukemia | Gemtuzumab ozogamicin | III | ISRCTN17161961† |
| (Mylotarg) |
BCL-2, B-cell CLL/lymphoma 2; BET, bromodomain and extraterminal; C-KIT, kit oncogene; CDK6, cyclin dependent kinase 6; hDOT1L, human disruptor of telomere silencing-1-like; IDH2, isocitrate dehydrogenase 2; XPO-1, exportin 1.
Examples are given where multiple trials for targeted agents exist.
Trials involve AML and non-AML patients. Also see text.