TABLE 2.
Key clinical trials’ efficacy data of ICIs in patients with mUC.
| Agent | Clinical trial | Phase | Line of therapy | Treatment arms | Efficacy outcomes | Median follow-up time | Publish year | Status |
|---|---|---|---|---|---|---|---|---|
| Pembrolizumab | KEYNOTE-012 | Phase b | First line | Pembrolizumab 10 mg/kg every 2 weeks | ORR 26% | 13 months | 2017 | Completed |
| mPFS 2 months | ||||||||
| mOS 13 months | ||||||||
| mDoR 10 months | ||||||||
| KEYNOTE-045 | Phase III | Second line | Pembrolizumab 200 mg every 3 weeks | mOS 10.3 months | 14.1 months | 2017 | Completed | |
| mPFS 2.1 months | ||||||||
| ORR 21.1% | ||||||||
| mDoR 3.5 months | ||||||||
| Investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine | mOS 7.4 months | |||||||
| mPFS 3.3 months | ||||||||
| ORR 11.4% | ||||||||
| mDoR 1.5 months | ||||||||
| KEYNOTE-052 (long-term outcomes) | Phase II | First line | Pembrolizumab 200 mg every 3 weeks | ORR 28.6% | 29.3 months | 2020 | Active, not recruiting | |
| mPFS 2.1 month | ||||||||
| mOS 11.3 months | ||||||||
| mDoR 30.1 months | ||||||||
| KEYNOTE-361 | Phase III | First line | Pembrolizumab plus chemotherapy | ORR 54.7% | NR | 2020 | Active, not recruiting | |
| mPFS 8.3 months | ||||||||
| mOS 17.0 months | ||||||||
| mDoR 8.5 months | ||||||||
| Pembrolizumab | ORR 30.3% | |||||||
| mPFS 3.9 months | ||||||||
| mOS 15.6 months | ||||||||
| mDoR 28.2 months | ||||||||
| Chemotherapy | ORR 44.9% | |||||||
| mPFS 7.1 months | ||||||||
| mOS 14.3 months | ||||||||
| mDoR 6.2 months | ||||||||
| HCRN GU14-182 | Phase II | Maintenance therapy | Pembrolizumab 200 mg every 3 weeks for up to 24 months | ORR 23.0% | 12.9 months | 2020 | Active, not recruiting | |
| mPFS 5.4 months | ||||||||
| mOS 22.0 months | ||||||||
| Placebo | ORR 10% | |||||||
| mPFS 3.0 months | ||||||||
| mOS 18.7 months | ||||||||
| Atezolizumab | IMvigor 210 cohort 1 | Phase II | First line | Atezolizumab 1,200 mg every 3 weeks | ORR 23% | 17.2 months | 2017 | Active, not recruiting |
| mPFS 2.7 months | ||||||||
| mOS 15.9 months | ||||||||
| mDoR NR | ||||||||
| IMvigor 210 cohort 2 | Phase II | Second line | Atezolizumab 1,200 mg every 3 weeks | ORR 15% | 11.7 months | 2017 | Active, not recruiting | |
| mPFS 2.1 months | ||||||||
| mOS 7.9 months | ||||||||
| mDoR NR | ||||||||
| IMvigor 211 (long-term outcomes) | Phase III | Second line | Atezolizumab 1,200 mg every 3 weeks | 24-months OS rate 23% | 33.0 months | 2021 | Completed | |
| Investigator’s choice of chemotherapy with paclitaxel, docetaxel, or vinflunine | 24-months OS rate 13% | |||||||
| IMvigor 130 | Phase III | First line | Atezolizumab plus platinum-based chemotherapy | ORR 47% | 11.8 months | 2020 | Active, not recruiting | |
| mPFS 8.2 months | ||||||||
| mDoR 8.5 months | ||||||||
| Atezolizumab 1,200 mg monotherapy | ORR 23% | |||||||
| mOS 15.7 months | ||||||||
| mDoR NR | ||||||||
| Placebo plus platinum-based chemotherapy | ORR 44% | |||||||
| mPFS 6.3 months | ||||||||
| mOS 13.1 months | ||||||||
| mDoR 7.6 months | ||||||||
| Nivolumab | CheckMate 032 (expansion cohort results) | Phase I/II | Second line | Nivolumab 3 mg/kg monotherapy every 2 weeks (N3) | ORR 25.6% | 24.5 months | 2019 | Recruiting |
| mPFS 2.8 months | ||||||||
| mOS 9.9 months | ||||||||
| Nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N3I1) | ORR 26.9% | |||||||
| mPFS 2.6 months | ||||||||
| mOS 7.4 months | ||||||||
| Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N1I3) | ORR 38.0% | |||||||
| mPFS 4.9 months | ||||||||
| mOS 15.3 months | ||||||||
| CheckMate 275 | Phase II | Second line | Nivolumab 3 mg/kg every 2 weeks | ORR 19.6% | 7.0 months | 2017 | Active, not recruiting | |
| mPFS 2.0 months | ||||||||
| mOS 8.7 months | ||||||||
| mDoR NR | ||||||||
| Durvalumab | Study 1108 UC cohort | Phase I/II | Second line | Durvalumab 10 mg/kg every 2 weeks for up to 12 months | ORR 17.8% | 5.8 months | 2017 | Completed |
| mPFS 1.5 months | ||||||||
| mOS 18.2 months | ||||||||
| mDoR NR | ||||||||
| DANUBE | Phase III | First line | Durvalumab 1,500 mg every 4 weeks | ORR 25.7% | 41.2 months | 2020 | Active, not recruiting | |
| mPFS 2.3 months | ||||||||
| mOS 13.2 months | ||||||||
| mDoR 9.3 months | ||||||||
| Durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks for four doses, followed by durvalumab maintenance (1,500 mg) every 4 weeks | ORR 36.3% | |||||||
| mPFS 3.7 months | ||||||||
| mOS 15.1 months | ||||||||
| mDoR 11.1 months | ||||||||
| Chemotherapy for up to six cycles | ORR 49.1% | |||||||
| mPFS 6.7 months | ||||||||
| mOS 12.1 months | ||||||||
| mDoR 5.7 months | ||||||||
| NCT02812420 | Phase Ⅰ | Second line | Durvalumab (1,500 mg kg−1) and tremelimumab (75 mg kg−1) every 4 weeks | Incidence of AEs | 19.2 months | 2020 | Active, not recruiting | |
| Avelumab | JAVELIN solid tumor | Phase Ⅰ | Second line | Avelumab 10 mg/kg every 2 weeks | ORR 17% | 9.9 months | 2017 | Completed |
| mPFS 1.5 months | ||||||||
| mOS 6.5 months | ||||||||
| mDoR NR | ||||||||
| JAVELIN Bladder 100 | Phase III | Maintenance therapy | Avelumab maintenance therapy 10 mg/kg every 2 weeks | ORR 9.7% | ≥19 months | 2020 | Active, not recruiting | |
| mPFS 3.7 months | ||||||||
| mOS 21.4 months | ||||||||
| mDoR 24.9 weeks | ||||||||
| Best supportive care alone (BSC) | ORR 1.4% | |||||||
| mPFS 2.0 months | ||||||||
| mOS 14.3 months | ||||||||
| mDoR 13.1 weeks | ||||||||
| Ipilimumab | NCT01524991 | Phase II | First line | Two cycles of gemcitabine plus cisplatin (GC) followed by four cycles of GC plus ipilimumab | ORR 69% | NR | 2017 | Completed |
| mPFS 7.9 months | ||||||||
| mOS 13.9 months | ||||||||
| mDoR 24.9 weeks | ||||||||
| Tremelimumab | NCT02527434 | Phase II | Second line | Tremelimumab monotherapy | ORR 18.8% | 9.3 months | 2019 | Active, not recruiting |
Abbreviations: ORR, overall response rate; mPFS, median progression-free survival; mOS, median overall survival; mDoR, median duration of response; NR, not reached or not reported.