Table 1 Clinical trials of PD-1/PD-L1 checkpoint blockades in glioblastoma

Neoadjuvant glioblastoma

NCT 02550249

29

Nivo+continued surgery

Primary and recurrent glioblastoma

PD-1

II

–

NCT 02852655

35

Pem + surgery+Pem

Recurrent/Progressive glioblastoma

PD-1

NA

–

NCT 02337686

18

Pem + surgery+Pem

Recurrent glioblastoma

PD-1

II

–

Newly diagnosed glioblastoma

NCT 02667587

550

Nivo+RT vs TMZ + RT

Unmethylated MGMT

PD-1

III

–

NCT 02617589

693

Nivo+RT + TMZ vs RT + TMZ

MGMT-methylated

PD-1

II

–

NCT 03047473

30

Ave + RT + TMZ

PD-L1

II

–

NCT 02530502

50

Pem + RT + TMZ

PD-1

I/II

–

NCT 02311920

32

Arm I: TMZ + Ipi;

Arm II: TMZ + Nivo;

Arm III: TMZ + Nivo+Ipi

PD-1/CTLA-4

I

–

NCT 03347097

40

PD-1-PIK T cells

PD-1

I

–

Recurrent glioblastoma

NCT 02658279

44

Pem

Hypermutator phenotype

PD-1

NA

–

NCT 02968940

43

Ave + HFRT

IDH mutant glioblastoma

II

–

NCT 02311582

58

Pem + MLA vs Pem

PD-1

I

–

NCT 02430363

58

Pem vs inhibitors of PI3K/Akt pathway

PD-1

I/II

–

NCT02054806

26

Pem

PD-L1 expression≥1%

PD-1

I

mPFS:2.8 m; mOS:14.4 m;

G3–4 TRAEs:15.4%

NCT 02336165

159

Arm A: MEDI4736 + RT;

Arm B: MEDI4736;

Arm B2: MEDI4736 + Bev (10 mg/Kg);

Arm B3: MEDI4736 + Bev (3 mg/Kg);

Arm C: MEDI4736 + Bev

Arm A: unmethylated MGMT

Arm B: Bev-naïve

Arm B2: Bev-naïve

Arm B3: Bev-naïve

Arm C: Bev-refractory

PD-L1/VEGF

II

ArmB:6 m-PFS:20%;

12 m-OS:44.4%;

G3–4 TRAEs:9.7%;

ArmC: OS≥22 week: 36%;

PFS ≥ 8 weeks: 50%;

G3–4 TRAEs: 4.5%

NCT 02337491

80

Pem + Bev vs Pem

PD-1/VEGF

II

Safety; mOS: 6.8 m

NCT 02794883

36

Dur vs Tre + Dur

PD-L1/CTLA-4

II

–

NCT 02017717

369

40

Nivo vs Bev

Nivo vs Nivo+Ipi

(Nivo3mg = 10; Nivo1mg + Ipi3mg = 10;

Nivo3mg + Ipi1mg = 20)

PD-1/CTLA-4/VEGF

III

I

mPFS: 1.5 m vs 3.5 m;

mOS: 9.8 m vs 10.0 m;

ORR: 8% vs 23%;

G3–4 TRAEs 18% vs 15%

Safety; Nivo3mg better

Tolerated than other combinations

12 m-OS: Nivo3mg: 40%;

Nivo1mg + Ipi3mg: 30%;

Nivo3mg + Ipi1mg: 35%

NCT 02658981

100

Arm A1: Anti-LAG-3;

Arm A2: Anti-CD137;

Arm B1: Anti-LAG3 + Nivo;

Arm B2: Anti-CD137 + Nivo

PD-1/LAG-3/CD137

I

–

NCT 02335918

175

Var + Nivo

PD-1/CD27

II

–

NCT 02937844

20

Anti-PD-L1 CSR T cells

PD-L1

I

–

OVT

NCT 02798406

48

DNX-2401+ Pem

Recurrent glioblastoma and GS

PD-1

II

–

Radiotherapy

NCT 02648633

4

Valproate+SRS + Nivo

Recurrent glioblastoma

PD-1

I

–

NCT 02313272

23

HFSRT+Pem + bev

High grade gliomas (III and IV)

PD-1/VEGF

I

6 m-OS:94%;12 m-OS:64%;

ORR:53%

NCT 02829931

26

HFSRT+Ipi + Nivo+Bev

Recurrent high grade gliomas

PD-1/CTLA-4/VEGF

I

–

NCT 02866747

62

HFSRT vs HFSRT+Dur

Recurrent glioblastoma

PD-L1

I/II

–

20

Pem/Nivo+RT

Recurrent high grade gliomas

PD-1

mPFS:4 m; mOS:10 m;

ORR:35%;

Tumor vaccines

NCT 02529072

7

Arm A: Nivo+surgery+Nivo and DC

vaccine;

Arm B: Nivo and DC vaccine+surgery

+ Nivo and DC vaccine

Recurrent high grade gliomas

PD-1

I

–

NCT 03422094

30

NeoVax+Nivo/NeoVax+Nivo+Ipi

Newly diagnosed glioblastoma

PD-1

I

–

NCT 03018288

108

RT + TMZ + Pem + HSPPC-96 vs RT + TMZ + Pem

Newly diagnosed glioblastoma

PD-1

II

–

NCT 03014804

30

DCVax-L vs DCVax-L + Nivo

Recurrent glioblastoma

PD-1

II

–

anti-CSF-1R

NCT 02526017

295

Cabiralizumab+Nivo

glioblastoma

PD-1

I

–