Table 2 Clinical trials affecting metabolic pathways in STS

MAPK pathways

RAF

Dabrafenib

Advanced solid tumors with BRAF mutations

Phase II

NCT02465060

[75]

[A]

[B]

Vemurafenib

Relapsed or refractory advanced solid tumors with BRAF V600 mutations

Phase II

NCT03220035

Dabrafenib + trametinib

MULTISARC

Phase III

NCT03784014

Dabrafenib + trametinib

BRAF V600E- mutated rare cancers

Phase II

NCT02034110

MEK1/2

Binimetinib + pexidartinib

Advanced GIST

Phase I completed

NCT03158103

[A]

[B]

[C]

Trametinib

Advanced solid tumors with BRAF mutations

Phase II

NCT02465060

Cobimetinib + MPDL3280A

Locally advanced or metastatic solid tumors

Phase I

NCT01988896

GDC-0941 + GDC-0973

Locally advanced or metastatic solid tumors

Phase II

NCT00996892

ERK1/2

Ulixertinib

STS, OS, EWS

Phase I/II

NCT03520075

[C]

PI3K/AKT/mTOR signaling

PIK3CA/mTOR

Samotolisib

STS

GIST

Phase I/II

NCT02008019

[C]

[76]

Pediatric sarcoma

Phase II

MATCH trial

NCT03458728

NCI MATCH EAY131-Z1F

[77]

[78]

GDC-0941

Locally advanced or metastatic solid tumors

Phase I

NCT00876109

[A]

GDC-0980

Locally advanced or metastatic solid tumors

Refractory solid tumors

Phase I

NCT00876122NCT00854152

NCT00854126

[A]

AKT/ERK

ONC201

Desmoplastic small round cell tumor

In vitro

[C]

GDC-0973 + GDC-0068

Locally advanced or metastatic solid tumors

Phase I

NCT01562275

[A]

mTOR

Sirolimus + pexidartinib

STS MPNST

Phase I/II

NCT02584647

[79]

[80]

[A]

Rapamycin + gemcitabine

OS

Phase II completed

NCT02429973

nanoparticle albumin-bound rapamycin + pazopanib

Advanced nonadipocytic soft tissue sarcomas

Phase I/II trial

NCT03660930

Lenvatinib + everolimus

Refractory pediatric solid tumors

Phase I/II

NCT03245151

CCI-779

STS/GIST

Phase II

NCT00087074

Cixutumumab + temsirolimus

Locally advanced, metastatic, or recurrent STS or bone sarcoma

Phase II

NCT01016015

CP-751,871 + RAD001

Advanced sarcomas and other malignant neoplasms

Phase I

NCT00927966

Everolimus

RAD001/progressive sarcoma

Phase II

NCT00767819

HIPPO

YAP/TAZ

Verteporfin

High histological grade

Reduced EWS metastatic potential

[81]

[82]

[83]

[84]

TCA CYCLE

IDH 1

IDH 1—AG-120

Chondrosarcoma

Phase I

NCT02073994

[85]

[86]

[87]

IDH 1—FT-2102

Advanced solid tumors

Active

NCT03684811

IDH 1—IDH305

Advanced malignancies with IDH1R132 mutations

Phase I

NCT02381886

IDH 1—BAY1436032

IDH1-mutant advanced solid tumors

Active

NCT02746081

AG-881

Advanced solid tumors with an IDH1 and/or IDH2 mutation

Phase I

NCT02481154

AG-120 + nivolumab

IDH1 mutant tumors

Phase II

NCT04056910

IDH2

IDH 2—AG-221

Advanced solid tumors

Phase I/II

NCT02273739

TCA cycle enzymes

Devimistat

STS

FDA orphan drug designation

[D]

Amino acids

ASS1 deficiency

ADI-PEG20 + gemcitabine + docetaxel

STS, OS, EWS

Phase II

NCT03449901

[88]

[89]

PDK

DCA

FS

Mice

[90]

GLS

CB-839—glutaminase inhibitor

GIST

Phase I completed

NCT02071862

[59]

Telaglenastat

NF1 mutation positive MPNST

Phase II

NCT03872427

Telaglenastat

 + talazoparib

Solid tumors

Phase I + phase II

NCT03875313

Heparan sulfate proteoglycans

Sulfen

EWS

Zebrafish model

[91]

NAMPT

FK866—MV87 inhibitors

FS

Mice

[92]

Folate receptor α

Pemetrexed

STS

Phase II

NCT04605770

[C]

Lipid metabolism

CPI-613

CCS

Phase II

NCT01832857

[A]

[E]