Table 2. Ongoing trials for immune checkpoint inhibitors in metastatic UC.
| Clinical trial number | Drug(s) investigated | Clinical setting | Study design | Phase | Primary endpoint |
|---|---|---|---|---|---|
| NCT02437370 [31] | Pembrolizumab+docetaxel or gemcitabine | Second- or third-line | Non-randomized, double arm | I | MTD |
| Arm A: pembrolizumab+docetaxel | |||||
| Arm B: pembrolizumab+gemcitabine | |||||
| NCT01524991 [32] | Ipilimumab+gemcitabine+cisplatin | Fist-line | Single-arm UC cohort | II | One-year OS |
| NCT02807636 (IMvigor130) [33] | Atezolizumab±gemcitabine/carboplatin or cisplatin | First-line | Randomized, double-blind, placebo-controlled, three-arm | III | PFS, OS, AEs |
| Arm 1: atezolizumab+gemcitabine/carboplatin or cisplatin | |||||
| Arm 2: placebo+gemcitabine/carboplatin or cisplatin | |||||
| Arm 3: atezolizumab alone | |||||
| NCT02853305 (KEYNOTE-361) [34] | Pembrolizumab±gemcitabine/carboplatin or cisplatin | First-line | Randomized, controlled, three arm | III | PFS, OS |
| Arm 1: pembrolizumab | |||||
| Arm 2: pembrolizumab+gemcitabine/carboplatin or cisplatin | |||||
| Arm 3: chemotherapy (gemcitabine/carboplatin or cisplatin) | |||||
| NCT03036098 (CheckMate-901) [35] | Nivolumab+ipilimumab or gemcitabine/cisplatin or carboplatin | First-line | Randomized | III | PFS, OS |
| Experimental group: nivolumab+ipilimumab or nivolumab+gemcitabine/cisplatin or carboplatin | |||||
| Comparator group: chemotherapy (gemcitabine/cisplatin or carboplatin alone) | |||||
| NCT02546661 [38] | Durvalumab±AZD4547 (FGFR tyrosine kinase inhibitor) | Second- or third-line | Randomized to durvalumab alone or the combination | I | AEs |
| NCT02443324 [39] | Pembrolizumab+ramucirumab (anti-VEGFR2 antibody) | Second-line and beyond | Non-randomized, single-arm for multiple tumors including UC | I | DLTs |
| NCT01928394 (CheckMate-032) [40] | Nivolumab±ipilimumab | Any line | Randomized, single arm for multiple tumors including UC | I/II | ORR |
| NCT02516241 (DANUBE) [41] | Durvalumab±tremelimumab | First-line | Three-arm randomization to durvalumab alone, durvalumab+tremelimumab, or chemotherapy (gemcitabine/cisplatin) | III | OS |
| NCT02608268 [42] | MBG453 (TIM-3 antagonist)+PDR001 (anti-PD-1 antibody) | Second-line and beyond | Non-randomized to MBG453 alone or MBG453 in combination PDR001 for multiple tumors including UC | I/II | AEs, ORR, DLTs |
| NCT01968109 [43] | Nivolumab±BMS-980616 (anti-LAG3 antibody) | Any line | Randomized, multiple tumor types including UC | I/II | AEs, ORR, DCR, DOR |
| Arm 1: BMS-980616 alone | |||||
| Arm 2: BMS-980616+nivolumab | |||||
| NCT02528357 [44] | Pembrolizumab±GSK3174998 (OX40 agonist) | Any line | Non-randomized, multiple tumor types including UC | I | AEs, DLTs |
| Part 1: GSK3174998 alone | |||||
| Part 2: GSK3174998+pembrolizumab | |||||
| NCT02178722 [48] | Pembrolizumab+epacadostat (indoleamine 2,3-dioxygenase inhibitor) | Second line and beyond | Single-arm, multiple tumor types including UC | I/II | DLTs, ORR |
| NCT02318277 [49] | Durvalumab+epacadostat | Second line and beyond | Single-arm, multiple tumor types including UC | I/II | DLTs, AEs, ORR |
| NCT02655822 [50] | Atezolizumab±CPI-444 (adenosine-A2A receptor antagonist) | Any line | Randomized, multiple tumor types including UC, dose selection study of CPI-444, 1 arm combining with atezolizumab | I | DLTs, ORR, AEs, MDL |
UC, urothelial carcinoma; PD-1, programmed cell death 1 receptor; MTD, maximum tolerated dose; OS, overall survival; PFS, progression-free survival; AE, adverse event; DLT, dose-limiting toxicity; ORR, objective response rate; DCR, disease control rate; DOR, duration of response; MDL, maximum dose level.