Table 1 Clinical trials of PD-1/PD-L1 checkpoint blockades in recurrent GB.
From: Immunotherapy for recurrent glioblastoma: practical insights and challenging prospects
Trials | No. | Arms | Characteristic | Target | Phase | Results |
|---|---|---|---|---|---|---|
NCT02550249 | 30 | Nivo+continued surgery | Primary and recurrent GB | PD-1 | II | mPFS:4.1 m; mOS:7.3 m; |
NCT02852655 | 35 | Pem+surgery+Pem | Recurrent/Progressive GB | PD-1 | I | mPFS:2.4 m; mOS:13.7 m; |
NCT02054806 | 26 | Pem | PD-L1 expression≥1% | PD-1 | I | mPFS:2.8 m; mOS:14.4 m; G3-4 TRAEs:15.4% |
NCT02336165 | 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:6m-PFS:20%; 12m-OS:44.4%; G3-4 TRAEs:9.7%; ArmC: OS ≥ 22week: 36%; PFS ≥ 8weeks: 50%; G3-4 TRAEs: 4.5% |
NCT02337491 | 80 | Pem+Bev vs Pem | PD-1/VEGF | II | Safety; mOS: 6.8 m | |
NCT02017717 | 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 12m-OS: Nivo3mg: 40%; Nivo1mg + Ipi3mg: 30%; Nivo3mg + Ipi1mg: 35% | |
NCT02866747 | 62 | HFSRT vs. HFSRT + Dur | Recurrent GB | PD-L1 | I/II | NA |
20 | Pem/Nivo+RT | Recurrent high-grade gliomas | PD-1 | mPFS:4 m; mOS:10 m; ORR:35%; | ||
NCT02794883 | 36 | Dur vs. Tre+Dur | PD-L1/CTLA-4 | II | NA | |
NCT02658981 | 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 | NA | |
NCT02335918 | 175 | Var+Nivo | PD-1/CD27 | II | NA | |
NCT02798406 | 48 | DNX-2401+ Pem | Recurrent GB and GS | PD-1 | II | NA |
NCT02648633 | 4 | Valproate+SRS + Nivo | Recurrent GB | PD-1 | I | NA |
NCT02829931 | 26 | HFSRT + Ipi+Nivo+Bev | Recurrent high-grade gliomas | PD-1/CTLA-4/VEGF | I | NA |
NCT02658279 | 44 | Pem | Hypermutator phenotype | PD-1 | NA | NA |
NCT02968940 | 43 | Ave+HFRT | IDH mutant GB | II | NA | |
NCT02311582 | 58 | Pem+MLA vs. Pem | PD-1 | I | NA | |
NCT02430363 | 58 | Pem vs. inhibitors of PI3K/Akt pathway | PD-1 | I/II | NA | |
NCT02337686 | 18 | Pem +surgery+Pem | Recurrent GB | PD-1 | II | NA |
NCT02529072 | 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 | NA |
NCT03493932 | 15 | Anti-LAG-3+Anti-PD-1 | Recurrent GB | LAG-3/PD-1 | I | No significant survival difference between responders and nonresponders |
NCT03532295 | 55 | Anti-IDO1 + Anti-PD-L1 + RT | Recurrent GB | IDO1/PD-L1 | I/II | NA |
NCT03665545 | 24 | Pem+IMA950 | Recurrent GB | PD-1/multi peptide | I/II | NA |
NCT03661723 | 60 | Pem+RT | Recurrent GB Arm A: Bev-naïve Arm B: Bev-refractory | PD-1 | II | NA |
NCT03743662 | 94 | Nivo+Bev+RT | Recurrent MGMT Methylated GB | PD-1 | II | NA |
NCT03233152 | 6 | Ipi+Nivo | Recurrent GB | CTLA-4/PD-1 | I | NA |
NCT03707457 | 30 | Nivo | Recurrent GB | PD-1 | I | NA |
NCT03341806 | 30 | Ave+Laser Interstitial Therapy | Recurrent GB | PD-L1 | I | NA |
NCT03291314 | 52 | Ave+Axitinib | Recurrent GB | PD-L1/VEGFR | II | NA |
NCT03430791 | 60 | TTF + Nivo+Ipi | Recurrent GB | PD-1/CTLA-4 | II | NA |
