Table 6

Large phase II and III clinical trials investigating ICIs for mUC

Results for immunotherapy treatment
TrialDesignInterventions (n patients)ORRMedian DOROSMedian PFS
IMvigor210, cohort I (NCT02951767)31 97Phase II, single-arm, open-labelAtezolizumab (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 97Phase II, single-arm, open-labelAtezolizumab (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)28Phase III, randomized, open-labelAtezolizumab 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)32Phase III, randomized, double-blindAtezolizumab 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)32Phase III, randomized, double-blindAtezolizumab+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-labelAvelumab maintenance vs best supportive care (n=700)9.7% (95% CI 6.8% to 13.3%)NRMedian 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)100Phase III, randomized, open-labelDurvalumab+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)113Phase II, single-arm, open-labelNivolumab (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-labelPembrolizumab (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)116Phase III, randomized, open-labelPembrolizumab (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)99Phase III, randomized, open-labelPembrolizumab+gemcitabine/platinum vs chemotherapy (first-line) (n=542)54.7%8.5 months1-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)106Phase II, randomized, double-blindPembrolizumab maintenance vs placebo (n=108)23%NRNR5.4 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.