Table 3:
Mechanisms of action of selected targeted agents under investigation for the treatment of pediatric cancer
| Approval in Adults | ||||||
|---|---|---|---|---|---|---|
| Drug Class | Example Agent(s)* | Target | Pediatric Intended Use | FDA | EMA | Pediatric Trial(s) |
| Tyrosine kinase inhibitors | Midostaurin Gliteritinib |
FLT3 | FLT3-altered AML |
Y Y |
Y Y |
NCT03591510 NCT04293562 |
| Crizotinib | ALK, ROS1 | IMT, ALCL NB |
Y | Y |
NCT01979536 NCT03126916 |
|
| Pazopanib Regorafenib |
VEGFR, PDGFR | Sarcoma | Y Y |
Y Y |
NCT02180867 NCT02389244 |
|
| Cabozantinib | MET, VEGFR, PDGFR |
Y | Y |
NCT02867592 NCT02243605 |
||
| Downstream signaling pathway inhibitors | Temsirolimus | mTOR | RMS | Y | Y | NCT02567435 |
| Vemurafenib | BRAF V600 | Biomarker (+) | Y | Y | NCT03220035 | |
| Dabrafenib + Trametinib |
BRAF + MEK | Low grade glioma High grade glioma |
Y | Y |
NCT02684058 NCT03919071 |
|
| Cobimetinib | MEK | Langerhans cell Histiocytosis | Y | Y | NCT04079179 | |
| Ruxolitinib* | JAK | CRLF or JAK altered ALL | Y | Y | NCT02913261 | |
| Developmental pathway inhibitors | Vismodegib Sonidegib |
SMO | SHH-driven medulloblastoma | Y Y |
Y Y |
NCT01878617 NCT04402073 |
| Epigenetic therapy | Panobinostat Vorinostat |
Histone deacetylase | DIPG (H3K27M) NB AML ALL |
Y Y |
Y N |
NCT02717455 NCT02035137 NCT03263936 NCT02553460 |
| Pinometostat | DOT1L | KMT2A-rearranged ALL | N | N | NCT03724084 | |
| SNDX-5613 | Menin | KMT2A-rearranged ALL or AML | N | N | NCT04065399 | |
| Azacitidine Decitabine |
DNA Methyl-transferases | KMT2A-rearranged ALL or AML | Y Y |
Y Y |
NCT02828358 NCT03263936 |
|
| Molibresib | Bromodomain (BET) | NUT Carcinoma | N | N | NCT04116359 | |
| Seclidemstat INCB059872 |
LSD1 | Ewing Sarcoma | N N |
N N |
NCT03600649 NCT03514407 |
|
| Cell death pathway inhibitors | Venetoclax | BCL-2 | AML ALL, AML, NHL |
Y | Y |
NCT03194932 NCT03236857 |
| Non-kinase fusion inhibitors | TK216 | EWS-FLI1 | Ewing sarcoma | N | N | NCT02657005 |
| Cell lineage monoclonal antibodies and antibody drug conjugates |
Rituximab | CD20 | NHL | Y | Y | NCT03206671 |
| Gemtuzumab | CD33 | AML | Y | Y | NCT02724163 | |
| Inotuzumab ozogamicin | CD22 | ALL | Y | Y | NCT02981628 | |
| Brentuximab vedotin | CD30 | Hodgkin ALCL |
Y | Y |
NCT02166463 NCT01979536 |
|
| Targeted radionuclides | Iodine-131-meta-iodo-benzylguanidine (MIBG) | Norepinephrine transporter | NB | N | N | NCT03126916 |
*
Not intended to be a comprehensive list of all agents under investigation.