Table 1 Clinical studies of recent targeted therapies for GBM, as single agent or in combination with standard of care. (Data from http://clinicaltrials.gov was searched until Nov 2023)

PDGFR

Olaratumab

–

2

rGBM

NCT00895180

(Completed)

-

Yes

PFS-6: 7.5%

Median: 34.3 weeks

VEGF

Bevacizumab

TMZ, RT

3

ndGBM

NCT05271240

(Recruiting)

-

Yes

Ongoing

Ongoing

Bevacizumab

TMZ, RT

3

rGBM

NCT02761070

(Active, not recruiting)

-

No

Ongoing

Ongoing

Bevacizumab

TMZ

2

GBM

NCT02898012

(Completed)

-

Yes

Median: 15.3 weeks

Median: 23.9 weeks

Vatalanib

TMZ, RT

1/2

ndGBM

NCT00128700

(Completed)

Well tolerated

Yes

Median: 7.2 months

Median: 16.2 months-

EGFR

Erlotinib

–

1

rGBM

NCT01257594

(Completed)

Unreported

-

-

-

Afatinib

TMZ, RT

1

ndGBM

NCT00977431

(Completed)

MTD: 30 mg with daily TMZ/RT and 40 mg with RT alone

-

-

-

Afatinib

TMZ

2

rGBM

NCT00727506

(Completed)

-

Yes

Median: 0.99 months, 1.53 months with TMZ

PSF-6: 3.0% and 10.3% with TMZ

Unreported

Afatinib

–

2

GBM

NCT00875433

(Completed)

-

No

Median: 10.6 weeks

Median: 39.6 weeks

Dacomitinib

–

2

rGBM

NCT01112527

(Completed)

-

No

Unreported

Unreported

Dacomitinib

–

2

rGBM

NCT01520870

(Completed)

-

Yes

Median: 2.7 months

PFS-6: 10.6%

Median: 7.4 months

Neratinib

–

2

GBM

NCT02977780

(Recruiting)

-

Yes

Median: 4.7 months

Median: 14.9 months

Cetuximab

RT

2

rGBM

NCT02800486

(Recruiting)

-

No

Ongoing

Ongoing

Cetuximab

–

1/2

ndGBM

NCT02861898

(Recruiting)

Yes

Ongoing

Ongoing

Cetuximab

RT, TMZ

2

ndGBM

NCT01044225

(Terminated, non-drug related)

-

No

Unreported

Unreported

STAT3

WP1066

–

1

rGBM

NCT01904123

(Completed)

MFD: 8 mg/kg

-

-

-

WP1066

RT

2

ndGBM

NCT05879250

(Not yet recruiting)

-

Yes

Ongoing

Ongoing

PI3K

Buparlisib

RT, TMZ

1

rGBM

NCT01473901

(Completed)

Not tolerable

-

-

-

Buparlisib

–

2

rGBM

NCT01339052

(Completed)

-

Yes

Median: 1.7 months

PFS-6: 8%

Median: 9.8 months

Sonolisib

–

2

GBM

NCT01259869

(Completed)

-

Yes

Median:

PFS-6: 17%

Unreported

mTOR

Everolimus

TMZ, RT

1/2

ndGBM

NCT01062399

(Completed)

Combining with TMZ increased toxicity

Yes

Median: 8.2 months

Median: 16.5 months

Sirolimus

–

1/2

GBM

NCT00047073

(Completed)

Tolerable

No

Unreported

Unreported

Metformin

TMZ

2

ndGBM

NCT04945148

(Not yet recruiting)

-

Yes

Ongoing

Ongoing

Vistusertib

–

1

rGBM

NCT02619864

(Completed)

Tolerable

-

-

-

AZD8055

–

1

rGBM

NCT01316809

(Completed)

Unreported

-

-

-

Onatasertib

–

1/2

Advanced solid tumours

NCT01177397

(Completed)

Tolerable

Yes

PFS-6: 0%

Unreported

RMC-5552

–

1/1b

rGBM

NCT05557292

(Active, not recruiting)

Ongoing

-

-

-

Sapanisertib

–

1

rGBM

NCT02133183

(Active, not recruiting)

Unreported

-

-

-

PI3K/mTOR

Paxalisib

RT, TMZ

2

ndGBM

NCT03522298

(Active, not recruiting)

-

Yes

Median: 8.4 months

Median: 15.7%

Voxtalisib

RT, TMZ

1

GBM

NCT00704080

(Completed)

MTD: 90 mg q.d. and 40 mg b.i.d. with TMZ

-

-

-

Proteasome

Bortezomib

TMZ

2

rGBM

NCT03643549

(Recruiting)

-

Yes

Ongoing

Median: 12.7 months for unmethylated, 21.7 months for methylated

Bortezomib

RT, TMZ

2

ndGBM

NCT00998010

(Completed)

-

Yes

Median: 6.2 months

Median: 19.1 months

Marizomib

RT, TMZ

1/2

ndGBM

NCT02903069

(Completed)

Tolerable

Yes

Unreported

Median: 14.8 months

Marizomib

RT, TMZ

3

ndGBM

NCT03345095

(Completed)

-

Yes

Median: 6.34 months

Median: 16.13 months

Disulfiram (+ Copper gluconate)

RT, TMZ

1

GBM

NCT01907165

(Completed)

Safe but can cause reversible neurological toxicities

-

-

-

Disulfiram (+ Copper gluconate)

TMZ

2

rGBM

NCT03034135

(Completed)

-

Yes

Median: 1.7 months

Median: 7.1 months

Disulfiram (+ Copper gluconate)

TMZ

2

Unmethylated GBM

NCT03363659

(Terminated, non-drug related)

-

No

PFS-6: 8.3%

69.2% after 1 year, 15.4% after 2 years

Disulfiram (+ Copper gluconate)

RT, TMZ

1/2

ndGBM

NCT02715609

(Active, not recruiting)

MTD: 375 mg/kg

Yes

Ongoing

Ongoing

PARP

Olaparib

TMZ

1

rGBM

NCT01390571

(Completed)

Tolerable

-

-

-

Olaparib/ Pamiparib

TMZ, RT

1/2

rGBM

NCT04614909

(Recruiting)

Ongoing

No

Ongoing

Ongoing

Olaparib

TMZ, RT

1/2

GBM

NCT03212742

(Recruiting)

Tolerable

No

Ongoing

Ongoing

Olaparib

–

Early 1

rGBM

NCT05432518

(Recruiting)

Ongoing

-

-

-

Olaparib

–

2

rGBM

NCT03212274

(Active, not recruiting)

-

Yes

Ongoing

Ongoing

Niraparib

–

2

rGBM

NCT05297864

(Active, not recruiting)

-

Yes

Ongoing

Ongoing

Niraparib

RT

2

rGBM

NCT04221503

(Active, not recruiting)

-

Yes

Ongoing

Ongoing

Niraparib

RT

2

rGBM

NCT04715620

(Unknown status)

-

No

Median: 157 days

PFS-6: 36%

Median: Ongoing

OS-6: 82.61%

Niraparib

RT

Early 1

ndGBM

NCT05076513

(Recruiting)

Tolerable

-

-

-

Niraparib

TMZ

Early 1

rGBM

NCT01294735

(Completed)

MTD: 40 mg niraparib + 150mg/m² TMZ

-

-

-

BSI-201

TMZ

1/2

ndGBM

NCT00687765

(Completed)

Unreported

No

Unreported

Unreported

BGB-290

TMZ

1/2

rGBM

NCT03914742

(Completed)

Unreported

Yes

Unreported

Unreported

BGB-290

TMZ

1

GBM

NCT03749187

(Recruiting)

Ongoing

-

-

-

Veliparib

TMZ, RT

2

ndGBM

NCT03581292

(Active, not recruiting)

-

No

Ongoing

Ongoing

Veliparib

TMZ, RT

1/2

ndGBM

NCT01514201

(Completed)

Tolerable

No

PFS-3: 2.9%

OS-3: 5.3%

Fluzoparil

TMZ

2

rGBM

NCT04552977

(Unknown status)

-

No

Unreported

Unreported

NMS-03305293

TMZ

1/2

rGBM

NCT04910022

(Recruiting)

Ongoing

Yes

Ongoing

Ongoing