Table 1.
Completed and ongoing ICB clinical trials in monotherapies and in combination with antiangiogenic therapy in GBM.
| Target | Treatment | Setting | Study Design | No. of Patients (n) | Primary Endpoint(s) | Primary Outcome | Identifier | Reference |
|---|---|---|---|---|---|---|---|---|
| PD-1 | Nivolumab vs. Bevacizumab |
R | Open-label phase III | 369 | OS | Primary endpoint not met | CheckMate-143 NCT02017717 |
[123] |
| PD-1 | Nivolumab + RT vs. TMZ + RT |
ND, unmethylated MGMT | Open-label phase III | 553 | OS | Primary endpoint not met | CheckMate-498 NCT02617589 |
[158] |
| PD-1 | Nivolumab + TMZ + RT vs. Placebo + TMZ + RT |
ND, methylated MGMT | Triple-blinded phase III | 693 (targeted) |
PFS, OS | Primary endpoints not met | CheckMate-548 NCT02667587 |
[159] |
| PD-1 | Pembrolizumab + TMZ + RT | ND | Open-label phase II | 56 (targeted) |
OS | Recruiting participants |
NCT03899857 | |
| CTLA-4 | Ipilimumab + Nivolumab | R | Open-label phase I | 27 | PFS, OS | mPFS 2.7 mo mOS 8.7 mo |
NCT03233152 | [131] |
| CTLA-4 | Ipilimumab + Nivolumab + RT vs. TMZ + RT |
ND, unmethylated MGMT | Open-label phase II/III | 485 (targeted) |
PFS, OS | Recruiting participants |
NCT04396860 | |
| LAG-3 | Anti-LAG-3 mAb (BMS-986016) +/− Nivolumab |
R | Open-label phase I | 33 | MTD | Late-onset DLT, DLT rate <33% |
NCT02658981 | [160] |
| TIGIT | Anti-TIGIT mAb (ASP8374) +/− Pembrolizumab |
Advanced solid tumors | Open-label phase Ib | 169 | Safety and tolerability: DLT and AE |
Result pending |
NCT03260322 | |
| TIGIT | Anti-TIGIT mAb (BMS-986207) +/− Nivolumab |
Advanced solid tumors | Open-label phase I/IIa | 130 (targeted) |
AE, SAE, ORR, mDOR, PSF rate | Recruiting participants |
NCT02913313 | |
| TIM-3 | Anti-TIM-3 mAb (MBG453) + spartalizumab + SRS |
R | Open-label phase I | 15 (targeted) |
SAE | Recruiting participants |
NCT03961971 | |
| PD-1 + VEGF | Pembrolizumab +/− Bevacizumab | R | Open-label, randomized phase II | 80 | MTD, DLT, PFS6 | MTD 200 mg/3 weeks No DLT PFS6 26% vs. 6.7% |
NCT02337491 | [161] |
| PD-L1 + VEGFR | Avelumab + Axitinib |
R | Open-label phase II (2 cohorts) | 54 | PSF6 | PSF6 22.2% vs. 18.5% |
NCT03291314 | [162] |
| PD-1 | Neoadjuvant +/− adjuvant Pembrolizumab |
R | Open-label, randomized phase II | 35 | PSF | mPFS 3.3 mo vs. 2.4 mo |
NCT02337686 | [163] |
| PD-1 | Neoadjuvant Nivolumab | ND & R | Open-label phase II | 30 | Changes in PD-L1 percentage and expression levels by lymphocytes | Nivolumab vs. control: no significant changes in immune cells’ PD-L1 expression |
NCT02550249 | [164] |
| PD-L1 | Durvalumab + RT (Cohort A) | ND, unmethylated MGMT (Cohort A) | Open-label, multi-cohort phase II | 40 | OS-12 | mOS 15.1 mo OS-12 60% |
NCT02336165 | [165] |
| PD-L1 + VEGF | Durvalumab +/− Bevacizumab (Cohort B) | R, bevacizumab- naïve |
Open-label, multi-cohort phase II | 97 | PFS-6 | PFS-6 B1: 20%; B2: 15.2%; B3: 21.1% |
NCT02336165 | [166] |
| Durvalumab + Bevacizumab (Cohort C) | R, bevacizumab- refractory |
Open-label, multi-cohort phase II | 22 | OS-6 | OS-6 36.4% ≥22 weeks | NCT02336165 | [167] | |
| PD-1 + VEGF | Neoadjuvant Nivolumab + low/standard Bevacizumab dosage | R | Open-label, randomized phase II | 90 | OS-12 | OS-12 58% | NCT03452579 | [168] |
Abbreviations: R, recurrent; ND, newly diagnosed; MGMT, O6-methylguanine-DNA methyltransferase; mo, months; OS, overall survival; OS-6, OS at 6 months; OS-12, OS at 12 months; mOS, median OS; PFS, progression-free survival; mPFS, median PFS; PFS6, 6 month PFS; RT, radiotherapy; TMZ, temozolomide; mAb, monoclonal antibody; MTD, maximum tolerated dose; DLT, dose-limiting toxicity; AE, adverse event; SAE, serious AE; ORR, objective response rate; mDOR, median duration of response; SRS, stereotactic radiosurgery.