Table 4.
Selection of current clinical trials in pediatric patients with brain tumors.
| Drug Type | Example Agents | Target | Disease | Pediatric Clinical Trial |
|---|---|---|---|---|
| Immunomodulators | APX005M | CD40 agonist | GBM, A, CNST, E, DIPG, MB | NCT03389802 |
| Pomalidomide | TNFa | CNSTS | NCT03257631 | |
| Indoximod | IDO, mTOR | E, MB, GBM, DIPG |
NCT05106296 NCT04049669 |
|
| NKTR-214 | CD122 IL2 pathway agonist | E, HGG, MB, PBTs | NCT04730349 | |
| Antibodies | Magrolimab | CD47 | PBTs | NCT05169944 |
| Avelumab | PD-L1 | CNSTs | NCT05081180 | |
| Nivolumab | PD-1 receptor | CNSTs |
NCT03838042 NCT04500548 |
|
| Ipilimumab | CTLA-4 | CNSTs | NCT04500548 | |
| Bevacizumab | VEGF-A | PBTs | NCT02698254 | |
| CAR T Cells and other cellular immunotherapies | HER2-specific CAR T cell locoregional Immunotherapy | HER2 | G, E, MB, GCT, ATRT, PB | NCT03500991 |
| EGFR806-specific CAR T cell locoregional Immunotherapy | EGFR | G, E, MB, GCT, ATRT, PNET, CPC, PB | NCT03638167 | |
| B7-H3-specific CAR T Cell locoregional Immunotherapy | B7H3 | DIPG, DMG, E, MB, GCT, ATRT, CPC, PB, G | NCT04185038 | |
| GD2-CART01 (iC9-GD2-CAR T-cells) | Disialoganglioside GD2 | MB, PBTs | NCT05298995 | |
| IL13Ralpha2-specific hinge-optimized 41BB-co-stimulatory CAR truncated CD19 | IL13Ralpha2 | PBTs | NCT04510051 | |
| Haploidentical transplant and donor NK cell infusion | CNSTs | NCT02100891 | ||
| Bone marrow-derived allogenic mesenchymal stem cells infected with an oncolytic adenovirus, ICOVIR-5 | pRB pathway | DIPG, MB | NCT04758533 | |
| Vaccines | PEP-CMV | CMV antigen | HGG, DIPG, MB | NCT03299309 NCT05096481 |
| Personalized neoantigen DNA vaccine | DMG, DIPG | NCT03988283 | ||
| rHSC-DIPGVax (neo-antigen heat schock protein vaccine) | DMG, DIPG | NCT04943848 | ||
| Dendritic cell vaccination: WT1 mRNA-loaded autologous monocyte-derived DCs | HGG DIPG | NCT04911621 | ||
| Immunomodulatory DC vaccine | DIPG, GBM | NCT03914768 | ||
| SurVaxM | Survivin | MB, GBM, AA, A, NOS, AO, AE, E, DIPG | NCT04978727 | |
| K27M peptide | DIPG, DMG | NCT02960230 | ||
| Viral Therapy | HSV G207 oncolytic herpes simplex virus-1 (HSV) | CNSTs | NCT03911388 NCT02457845 | |
| Wild-type reovirus (reolysin) | HGGs | NCT02444546 | ||
| Polio/rhinovirus recombinant (PVSRIPO) | CD155 nectin-like molecule-5 | CNSTs | NCT03043391 | |
| DNX-2401 oncolytic adenovirus | Integrins | BSG, DIPG | NCT03178032 | |
| Conventional chemotherapeutics | Mebendazole: | Tubulin | MB, A, GB, AA, Brain Stem Neoplasms, O, AO, G | NCT02644291 |
| PTC596 | Tubulin | DIPG, HGG | NCT03605550 | |
| Antimetabolites | Pemetrexed | Folate analog | MB | NCT01878617 |
| Hydroxyurea | RRM2 | G, GBM | NCT03463733 | |
| New chemotherapeutics | Marizomib | Proteasome | DIPG, BSG, PBTs | NCT04341311 |
| ALRN-6924 | MDM2/MDMX | PBTs | NCT03654716 | |
| Curaxin CBL0137 | FACT | DMG, DIPG, CNSTs | NCT04870944 | |
| Kinase Inhibitors | CX-4945 silmitasertib | CK2 | MB | NCT03904862 |
| Prexasertib | Chk1 | MB | NCT04023669 | |
| 9-ING-41 | GSK 3β | PBTs | NCT04239092 | |
| Trametinib | MEK1, MEK2 | PBTs | NCT03434262 | |
| Ibrutinib | Bruton’s tyrosine Kinase | E, MB, GBM | NCT05106296 | |
| Lenvatinib | VEGFR1, 2 and 3, FGFR1, 2, 3 and 4, PDGFR alpha, c-Kit, RET proto-oncogene | CNSTs |
NCT05081180 NCT03245151 |
|
| Alectinib | ALK | CNSTs | NCT04774718 | |
| Larotrectinib | Tropomyosin receptor kinases | CNSTs |
NCT03213704 NCT03834961 NCT03155620 |
|
| Repotrectinib (TPX-0005) | ALK, ROS | CNSTs | NCT04094610 | |
| Downstream signaling pathway inhibitors | Vemurafenib | B-Raf. BRAFV600 | G | NCT01748149 NCT03220035 |
| Entrectinib | TRKA, TRKB, TRKC, ROS1, ALK | CNSTs | NCT02650401 | |
| ONC206 | Stress response, DRD2/ClpP | DMG, CNSTs | NCT04732065 | |
| Everolimus immunosupr | mTor, FKBP-12 | HGG, PNET | NCT03245151 | |
| Sirolimus immunosupr | mTor, FKBP-12 | CNSTs | NCT02574728 | |
| GDC-0084 | PI3K/mTor | CNSTs | NCT03696355 | |
| WP1066 | JAK/STAT3 | PBTs | NCT04334863 | |
| Indoximod | IDO, mTOR | E, MB, GBM | NCT05106296 | |
| MEK162 | Ras/Raf/MEK | LGG | NCT02285439 | |
| Trametinib | MEK1/2 | PBTs |
NCT04485559 NCT03363217 NCT05180825 NCT02684058 NCT04201457 |
|
| Developmental pathway inhibitors | Vismodegib | SMO | MB | NCT01878617 |
| Cell Death Pathway inducers | ONC201 | TRAIL, ISR | DIPG, DMG, HGG |
NCT05009992 NCT05580562 |
| Angiogenesis inhibitor | Recombinant human endostatin (rh-ES) | Ras, Raf, VEGF, VEGFR2 | LGG | NCT04659421 |
| Epigenetic therapy | BMS-986158 and BMS-986378 | Bromodomain (BRD) and extra-terminal domain (BET) | PBTs | NCT03936465 |
| RRx-001 | DNMT and global methylation | PBTs | NCT04525014 | |
| Panobinostat | HDAC | DIPG, BSG, PBTs |
NCT02717455 NCT04341311 |
|
| MRT/ATRT | NCT04897880 | |||
| Entinostat | Class I and IV HDAC | CNSTs | NCT03838042 | |
| Tazemetostat | EZH2 | CNSTs | NCT03213665 | |
| Vorinostat | HDAC | BSG, A, CAA, CSCN | NCT01236560 | |
| BMS-986158 | Bromodomain and extra-terminal (BET) proteins | PBTs |
NCT03936465 |
|
| Melitherapy | 2-hydroxyoleic acid | Plasma membrane composition | PBTs | NCT04299191 |
| BXQ-350 | Plasma membrane sphingolipid modulation | DIPG, DMG PBTs |
NCT04771897 NCT04404569 |
|
| Radiolabeled drugs | Radiolabeled phospholipid drug conjugate: CLR 131 radioiodinated phospholipid ethers (PLEs) | Lipid rafts of cancer cell membranes | PBTs, | NCT03478462 |
| Peptide receptor radionuclide: lutathera (177Lu-DOTATATE) | Somatostatin receptors | CNSTs | NCT05278208 | |
| Radiolabelled monoclonal antibody: iodine I 131 MOAB 8H9 | 4Ig-B7-H3 | CNSTs | NCT00089245 |
Abbreviations: A: astrocytoma, AA: anaplastic astrocytoma, AE: anaplastic ependymoma, ATRT: atypical teratoid rhabdoid tumor, AO: anaplastic oligodendroglioma, BSG: brain stem glioma, CAA: cerebellar anaplastic astrocytoma, Chk1: checkpoint kinase 1, CK2: protein casein kinase II, ClpP: human mitochondrial caseinolytic protease P, CNSTs: central nervous system tumors, CPC: choroid plexus carcinoma, CSCN: childhood spinal cord neoplasm, DIPG: diffuse intrinsic pontine glioma, DMG: diffuse midline gliomas, DNMT: DNA methyltransferase, DRD2: dopamine receptor D2, E: ependymoma, G: glioma, FACT: facilitates chromatin transcription complex, G: glioma, GBM: glioblastoma multiforme, GCT: germ cell tumor, HDAC: histone deacetylase, HGG: high-grade glioma, IDO: indoleamine 2,3-dioxygenase, ISR: TRAIL, integrated stress response LGG: low-grade glioma, MB: medulloblastoma, MRT: malignant rhabdoid tumor, O: oligodendroglioma, PB: pineoblastoma, PBTs: pediatric brain tumors, PD-L1: programmed death-ligand 1, pRB: retinoblastoma tumor suppressor protein, RRM2: M2 protein subunit of ribonucleotide reductase.