Large phase II and III clinical trials investigating ICIs for mUC
| Results for immunotherapy treatment | ||||||
| Trial | Design | Interventions (n patients) | ORR | Median DOR | OS | Median PFS |
| IMvigor210, cohort I (NCT02951767)31 97 | Phase II, single-arm, open-label | Atezolizumab (first-line) (n=119) | 24% (95% CI 16% to 32%) | Median not reached (2-year follow-up) | 2-year OS 41% (95% CI 32% to 50%) | 2.7 months (95% CI 2.1 to 4.2) |
| IMvigor210, cohort II (NCT02108652)17 97 | Phase II, single-arm, open-label | Atezolizumab (R/R) (n=310) | 16% (95% CI 13% to 21%) | 27.7 months (95% CI 2.1 to 33.4) | 2-year OS 23% (95% CI 19% to 28%) | 2.1 months (95% CI 2.1 to 2.1) |
| IMvigor211 (NCT02302807)28 | Phase III, randomized, open-label | Atezolizumab vs chemotherapy (R/R) (n=931) | PD-L1 IC2/3: 23% ITT: 13.4% | PD-L1 IC2/3: 15.9 months (95% CI 10.4 to NE) ITT: 12.7 months (95% CI 13.0 to 21.7) | Median OS PD-L1 IC2/3: 11.1 months (95% CI 8.6 to 15.5) ITT: 8.6 months (95% CI 7.8 to 9.6) Stratified HR 0.87 (95% CI 0.63 to 1.21; p=0.41) | PD-L1 IC2/3: 2.4 months (95% CI 2.1 to 4.2) ITT: 2.1 months (95% CI 2.1 to 2.2) |
| IMvigor130 (NCT02807636)32 | Phase III, randomized, double-blind | Atezolizumab vs chemotherapy (first-line) (n=451) | 23% (95% CI 19% to 28%) | NE (95% CI 15.9 months to NE) | Median OS 15.7 months (95% CI 13.1 to 17.8) Stratified HR 0.83, (95% CI 0.69 to 1.00; one-sided p=0.027) | NR |
| IMvigor130 (NCT02807636)32 | Phase III, randomized, double-blind | Atezolizumab+gemcitabine/platinum (first-line) vs chemotherapy (n=362) | 47% (95% CI 43% to 52%) | 8.5 months (95% CI 7.2 to 10.4) | Median OS 16.0 months (95% CI 13.9 to 18.9) HR (1.02 95% CI 0.83 to 1.24) | 8.2 months (95% CI 6.5 to 8.3) Stratified HR 0.82 (95% CI 0.70 to 0.96; one-sided p=0.007) |
| JAVELIN Bladder100 (NCT02603432)37 | Phase III, randomized, open-label | Avelumab maintenance vs best supportive care (n=700) | 9.7% (95% CI 6.8% to 13.3%) | NR | Median OS 21.4 months (95% CI 18.9 to 26.1) HR 0.69 (95% CI 0.56 to 0.86; p=0.001) | 3.7 months (95% CI 3.5 to 5.5) HR 0.62 (95% CI 0.52 to 0.75) |
| DANUBE (NCT02516241)100 | Phase III, randomized, open-label | Durvalumab+tremelimumab vs chemotherapy (first-line) (n=1,126) | 36% | 11.1 months (95% CI 7.9 to 18.5) | Median OS 15.1 months (95% CI 13.1 to 18.0) Durvalumab monotherapy HR 0.89 (95% CI 0.71 to 1.11; p=0.30) Durvalumab+tremilumab HR 0.85 (95% CI 0.72 to 1.02; p=0.075) | NR |
| CheckMate 275 (NCT02387996)113 | Phase II, single-arm, open-label | Nivolumab (R/R) (n=386) | 20.7% (95% CI 16.1% to 26.1%) | 20.3 months (95% CI 11.5 to 31.3) | 3-year OS 22%; Median OS 8.6 months (95% CI 6.1 to 11.3) | 1.9 months (95% CI 1.9 to 2.3) |
| KEYNOTE-052 (NCT02335424) 156 157 | Phase II, single-arm, open-label | Pembrolizumab (first-line) (n=374) | 24% (95% CI 20% to 29%) | Median not reached (1-year follow-up) | 1-year OS 47.5% | 2 months (95% CI 2 to 3) |
| KEYNOTE-045 (NCT02256436)116 | Phase III, randomized, open-label | Pembrolizumab (R/R) (n=542) | 21.1% (95% CI 16.4% to 26.5%) | Median not reached (2-year follow-up) | 2-year OS 26.9% HR 0.70 (95% CI 0.57 to 0.85; p<0.001) | 2.1 months (95% CI 2.0 to 2.2) HR 0.96 (p = 0.32) |
| KEYNOTE-361 (NCT02853305)99 | Phase III, randomized, open-label | Pembrolizumab+gemcitabine/platinum vs chemotherapy (first-line) (n=542) | 54.7% | 8.5 months | 1-year OS 61.8% HR 0.86 | 8.3 months (95% CI 7.5 to 8.5) HR 0.78 (p=0.0033) |
| HCRN GU14-182 (NCT02500121)106 | Phase II, randomized, double-blind | Pembrolizumab maintenance vs placebo (n=108) | 23% | NR | NR | 5.4 months (95% CI 3.1 to 7.3) |
CI, confidence interval; DOR, duration of response; HR, hazard ratio; ICI, immune checkpoint inhibitor; ITT, intent-to-treat; mUC, metastatic urothelial cancer; NE, not estimable; NR, not reported; ORR, overall response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PD-L1 IC2/3, PD-L1 expression in ≥5% of tumor-infiltrating immune cells; PFS, progression-free survival; R/R, relapsed/refractory.