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

From: Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma

Setting Trials No. Arms Characteristic Target Phase Results
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
  1. GS Gliosarcoma, Nivo Nivolumab, Anti-PD-1 Antibody, Pem Pembrolizumab, Anti-PD-1 Antibody, TMZ Temozolomide, Ave Avelumab, Anti-PD-L1 Antibody, PD-1-PIK T cells Pluripotent immune killer T cells express PD-1 antibody, HFRT Hypofractionated radiation therapy, IDH Isocitrate Dehydrogenase, MLA MRI-guided laser ablation, Ipi Ipilimumab, Anti-CTLA-4 Antibody, VEGF Vascular endothelial growth factor, Tre Tremelimumab, Anti-CTLA-4 Antibody, Dur Durvalumab, Anti-PD-L1 Antibody, Var Varlilumab, Anti-CD27 Antibody, OVT Oncolytic virotherapy, HFSRT Hypofractionated stereotactic irradiation, Anti-PD-L1 CSR T cells Autologous Chimeric Switch Receptor Engineered T Cells Redirected to PD-L1, DNX-2401 A genetically modified oncolytic adenovirus, DC Dendritic cell, HSPPC-96 a vaccine made from fresh tumor taken at the time of surgery, DCVax-L Autologous DC pulsed with tumor lysate antigen Vaccine, Cabiralizumab Anti-CSF-1R antibody