Table 1.
General overview of currently enrolling studies.
| NCT (Title), Ref | Phase | N | ICI (CP) | Chemotherapy | Radiotherapy | Concurrent/Adjuvant | Primary Endpoint | Secondary Endpoints |
|---|---|---|---|---|---|---|---|---|
| NCT03620435 (Marcq et al.) [31] | I | 8 | Atezolizumab (PD-L1) | Gem | 20 × 2.5 Gy and 20 × 2 pelvic nodes IMRT | Concurrent + adjuvant 9 m |
Safety/toxicity | RR, OS, QoL |
| NCT03844256 (CRIMI) [32] | Ib/II | 30–50 | Nivolumab (PD-1) +/− Ipilimumab (CTLA-4) | MMC + Cape | 20 × 2 Gy whole bladder, tumor boost 20 × 0.75 Gy | Concurrent + 1 y adjuvant nivolumab |
Safety/toxicity | DFS, OS |
| NCT03171025 (NEXT) [36] | II | 28 | Nivolumab (PD-1) | Radiosensitizing NOS | NR | Adjuvant 1 y | Failure free survival | BI-EFS, AE Cystectomy rate QoL |
| NCT03993249 [37] | II | 78 | Nivolumab (PD-1) | SoC | SoC | Concurrent | Locoregional control rate | AE, RFS, OS, QoL |
|
NCT02662062 (ANZUP 1502) [33] |
II | 30 | Pembrolizumab (PD-1) | Cis | 32 × 2 Gy | Concurrent | Safety/toxicity | RR, MFS, Cystectomy rate |
| NCT02621151 (15-00220) [39] | II | 54 | Pembrolizumab (PD-1) | Gem | 20 × 2.6 Gy | Concurrent | BI-DFS | AE, RR, MFS, OS |
| NCT04216290 (INSPIRE) [35] | II | 114 | Durvalumab (PD-L1) | Gem or Gem + Carbo or Gem + Cis or MVAC | 6.5–8 weeks NOS |
Concurrent + 9 m adjuvant | Complete response rate | BI-EFS, Cystectomy rate, PFS, MFS, CSS, OS |
| NCT03768570 (BL13) [38] | II | 190 | Durvalumab (PD-L1) | Cis or 5-FU + MMC or Gem | Bladder: 32 × 2 Gy or 20 × 2.5 Gy. Pelvis: 45–46 Gy + 17–20 Gy bladder |
Adjuvant 1 y | DFS | BI-EFS, locoregional control, MFS |
| NCT03697850 (BladderSpar) [40] | II | 77 | Atezolizumab (PD-L1) | SoC | ≥60 Gy | Adjuvant 1 y | DFS | Local control, AE, DFS, OS, QoL |
| NCT04241185 (Keynote-992) [34] | III | 636 | Pembrolizumab (PD-1) | Cis or 5-FU + MMC or Gem | 32 × 2 Gy +/− Nodes or 20 × 2.75 Gy | Concurrent + 1 y adjuvant | BI-EFS | AE, OS, MFS. NMIBC recurrence, QoL |
|
NCT05072600 (2021-305) [41] |
III | 54 | Pembrolizumab (PD-1) | SoC | SOC | Adjuvant 1 y | PFS | NR |
| NCT03775265 (INTACT) [42] | III | 475 | Atezolizumab (PD-L1) | Cis or 5-FU + MMC or Gem | Bladder or Pelvis | Concurrent + 6 m adjuvant | BI-EFS | AE, OS, QoL |
NCT: national clinical trial number, ICI: immune checkpoint inhibitors, DFS: disease-free survival, OS: overall survival, RR: response rate, MFS: metastatic free survival, AE: adverse events, BI-EFS: bladder intact event-free survival, NMIBC: non-muscle-invasive bladder cancer, QoL: quality of life, PFS: progression-free survival, CSS: cancer-specific survival, CP: Checkpoint targeted, MMC: mitomycin C, Cape: capecitabine, Cis: cisplatinum, 5-FU: fluorouracil, Carbo: carboplatin, MVAC: methotrexate vinblastine, adriamycin, cisplatinum, SoC: standard of care, Gy: gray, NOS: not otherwise specified, NR: not reported, IMRT: intensity-modulated radiation therapy, PD-1: programmed death 1, PD-L1: programmed death-ligand 1, CTLA-4: cytotoxic T lymphocyte antigen-4, Gem: gemcitabine.