Table 10.

Selected targeted treatments for pediatric solid tumours—authorized or under development.

Specific Gene Mutation/Alteration	Targeted Treatment	Development Phase	Clinical Trial Identifier	Target Population
ALK alterations: -fusions -point mutations	AKL- inhibitors:	Phase I/II	NCT00939770	Anaplastic lymphoma kinase (ALK) positive tumors, relapsed or refractory solid tumors or anaplastic large cell lymphoma,
	Crizotinib	Phase II/III	NCT03874273	inflamatory myofibroblastic tumor
		Phase III	NCT03126916	neuroblastoma
		Phase II	NCT02034981	patients harboring an alteration on ALK, MET or ROS1
	Ensartinib	Phase II	NCT03213652	Relapsed or refractory advanced solid tumors, Non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 alterations
Anti-CD 20 antibody	Rituximab	Authorized	-	Mature B cell Lymphoma
Anti-GD 2 antibody	Dinutuximab	Authorized	-	Neuroblastoma
Anti-CD-30 antibody	Brentuximab Vedotin	Phase III	NCT02166463 NCT01979536	Hodgkin Lymphoma ALCL
BRAF alterations: -point mutations (including p.V600E) -Fusions (KIAA1549:BRAF)	Dabrafenib	Phase I/II	NCT01677741	Advanced BRAF V600 mutation-positive solid tumors
	Dabrafenib + Trametinib	Phase II	NCT02684058	BRAF V600 mutation positive low grade glioma or relapsed or refractory high grade glioma
	Vemurafenib	Phase II	NCT03220035	Relapsed or refractory advanced solid tumors, Non-Hodgkin Lymphoma, or histiocytic disorders with BRAF V600 mutations, Langerhans cell histiocytosis (LCH), and other histiocytic disorders.
	Cobimetinib	Phase II	NCT04079179	Refractory langerhans cell histiocytosis (LCH), and other histiocytic disorders.
	Trametinib	Phase II	NCT03363217	Pediatric neuro-oncology patients with refractory tumor and activation of the MAPK/ERK pathway
	Selumetinib	Phase III	NCT04576117	Recurrent or progressive low-grade glioma
CDKN2A/B deletion	Palbociclib	Phase II	NCT03526250	Rb positive advanced solid tumors, Non-Hodgkin Lymphoma, or histiocytic disorders with activating alterations in cell cycle genes
	Ribociclib with Everolimus	Phase I	NCT03387020	Recurrent or refractory malignant brain tumors
EZH2 alterations	Tazemetostat	Authorized	-	Epithelioid sarcoma ≥16 years
FGRF alterations	Erdafitinib	Phase II	NCT03210714	Patients with relapsed or refractory advanced solid tumors, Non-Hodgkin lymphoma, or histiocytic disorders with FGFR alterations
H3-3A, HIST1H3B, HIST1H3BC point mutation	Panobinostat	Phase I	NCT02717455	DIPG (H3K27M)
	Vorinostat	Phase II	NCT02035137	Neuroblastoma
	GD2 CART-cell	Phase I	NCT03635632	Relapsed or refractory neuroblastoma and other GD2 positive cancers
LSD1	Seclidemstat	Phase I	NCT03600649	Ewing or Ewing-related sarcomas
MEK alterations	Cobimetinib	Phase I/II	NCT02639546	Gliomas, sarcomas, neuroblastoma, melanoma, MPNST, rhabdoid tumors, including atypical teratoid/rhabdoid tumor (AT/RT), NF1-associated tumors or RASopathy-associated tumors
	Selumetinib	Phase III	NCT04576117	Recurrent or progressive low-grade glioma
		Authorized	-	Plexiform neurofibroma
MET: -amplifications -fusions	Volitinib	Phase I	NCT03598244	Recurrent or refractory primary CNS tumors
mTOR pathway genes alterations, including TSC1, TSC2	Everolimus	Authorized	-	Subependymal giant cell astrocytoma (SEGA)
	Temsirolimus	Phase III	NCT02567435	Rhabdomyosarcoma
NTRK gene fusions	Vitrakvi/Larotrectinib Entrectinib	Authorized	-	Treatment of adult and paediatric patients with solid tumours that display a neurotrophic tyrosine receptor kinase (NTRK) gene fusion
PARP alterations	Olaparib	Phase I	NCT04236414	Pediatric solid tumours
PD-1/PD-L1	Pembrolizumab	Authorized	-	R/R classic Hodgkin Lymphoma, melanoma ≥12 years
	Ipilimumab	Authorized	-
	Pembrolizumab	Phase I	NCT02359565	Recurrent, progressive, or refractory high-grade gliomas, diffuse intrinsic pontine gliomas, hypermutated brain tumors, ependymoma or medulloblastoma
	Nivolumab	Phase II	NCT03173950	Medulloblastoma, ependymoma, choroid plexus tumors, atypical/malignant meningioma
RET alterations	Selpercatinib	Authorized	-	Treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC)
ROS1 fusions	Repotrectinib	Phase I/II	NCT04094610	Pediatric and young adult subjects harboring ALK, ROS1, or NTRK1/2/3
	Entrectinib	Phase I/II	NCT02650401	Locally advanced or metastatic solid or primary CNS tumors
	Ensartinib	Phase II	NCT03213652	Relapsed or refractory advanced solid tumors, non-hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 alterations
SMARCB1 -point mutations -CNVs	Tazemetostat	Phase I	NCT02601937	Rhabdoid tumors, INI1-negative tumors
SMO alterations	Vismodegib	Phase II	NCT01878617	Medulloblastoma SHH subtype
			NCT01601184
	Sonidegib	Phase I/II	NCT01125800	Medulloblastoma, advanced pediatric solid potentially dependent on the Hedgehog-signaling pathway
VEGFR, PDGFR alterations	Pazopanib	Phase II	NCT01956669	Pediatric solid tumors
	Regorafenib	Phase II	NCT02048371	Selected sarcoma subtypes: (Ewing sarcoma, rhabdomyosarcoma, osteosarcoma)
VEGFR1, VEGFR3, FGFR3, FGFR4, PDGFRA alterations	Lenvatinib	Phase I/II	NCT02432274	Refractory or relapsed solid malignancies