Table 1. Selected trials in locally advanced/metastatic urothelial carcinoma with available results.
| Trial | Phase | Inclusion criteria | Experimental
arm(s) |
Patients
enrolled |
ORR,
percentage |
DCR,
percentage |
Median
follow-up, months |
mPFS,
months |
mOS,
months |
mDOR,
months |
Status |
|---|---|---|---|---|---|---|---|---|---|---|---|
| KEYNOTE-045
NCT02256436 |
III | LA/mUC with
progression post- platinum |
Pembrolizumab | 270 | 21.1 | 38.5 | 27.7 | 2.1
HR 0.96 (0.79–1.16) |
10.1
HR 0.70 (0.57–0.85) |
NR | Results
published |
| Chemotherapy
(paclitaxel, docetaxel, or vinflunine) |
272 | 11 | 44.9 | 27.7 | 3.3 | 7.3 | 4.4 | ||||
| CheckMate
032 NCT01928394 |
I/II | LA/mUC with
progression post- platinum or refused chemo |
Nivolumab 3 mg/kg
(NIVO3) |
78 | 25.6 | 52.5 | 2.8 | 9.9 | 30.5 | Results
published |
|
| Nivolumab 3 mg/kg
+ ipilimumab 1 mg/ kg (NIVO3+IPI1) |
104 | 26.9 | 50 | 2.6 | 7.4 | 22.3 | |||||
| Nivolumab 1 mg/kg
+ ipilimumab 3 mg/ kg (NIVO1+IPI3) |
92 | 38 | 63 | 4.9 | 15.3 | 22.9 | |||||
| IMvigor211
NCT02302807 |
III | LA/mUC with
progression post- platinum (analysis of IC2/3 population) |
Atezolizumab | 116 | 23 | 43 | 2.4
HR 1.01 (0.75–1.34) |
11.1
HR 0.87 (0.63–1.21) |
15.9 | Results
published |
|
| Chemotherapy
(paclitaxel, docetaxel, or vinflunine) |
118 | 22 | 54 | 4.2 | 10.6 | 8.3 | |||||
| IMvigor130
NCT02807636 |
III | 1L mUC, platinum-
eligible |
Arm A:
atezolizumab + PBC |
451 | 47 | 11.8 | 8.2
HR 0.82 (0.7–0.96) |
16
HR 1.02 (0.83–1.24) |
Preliminary
results presented |
||
| Arm B:
atezolizumab monotherapy |
362 | 23 | |||||||||
| Arm C: placebo +
PBC |
400 | 44 | 11.8 | 6.3 | 13.4 | ||||||
| PIVOT-02
NCT02983045 |
I/II | 1L mUC, cisplatin-
ineligible or refuses |
NKTR-214 +
nivolumab |
34 | 48 | 70 | Preliminary
results presented |
||||
| HCRN
GU14-182 NCT02500121 |
II | LA/mUC with at
least SD on 1L PBC |
Maintenance
pembrolizumab |
55 | 23 | 58 | 12.9 | 5.4
HR 0.65 |
22
HR 0.91 (0.52–1.59) |
Results
published |
|
| Placebo | 52 | 10 | 39 | 12.9 | 3.0 | 18.7 | |||||
| Javelin
Bladder 100 NCT02603432 |
III | LA/mUC with at
least SD on 1L PBC |
Maintenance
avelumab + BSC |
350 | 9.7 | 41.1 | 3.7
HR 0.62 (0.52–0.75) |
21.4
HR 0.69 (0.56–0.86) |
Preliminary
results presented |
||
| BSC alone | 350 | 1.4 | 27.4 | 2.0 | 14.3 | ||||||
| BLC2001
NCT02365597 |
II | mUC with
progression post- chemotherapy and FGFR2/3 alteration |
Erdafitinib | 101 | 40 | 24 | 5.5 | 11.3 | 6 | Results
published |
|
| NCT01004224 | I | LA/mUC with
progression post-platinum or contraindication to PBC and FGFR3 alteration |
Infigratinib | 67 | 25.4 | 64.2 | 3.75 | 7.75 | 5.06 | Results
published |
|
| NCT02122172 | II | LA/mUC with
progression post- platinum |
Afatinib | 23 | 8.6 | 39 | 1.4 | 5.3 | Results
published |
||
| NCT02236195 | II | LA/mUC with
progression post-platinum and CREBBP or EP300 mutation or deletion |
Mocetinostat | 17 | 11 | 33 | 57 days | 3.5 | Results
published |
||
| EV-101
NCT02091999 |
I | Part A: mUC
with progression post-platinum or cisplatin-ineligible Part B: mUC with renal insufficiency Part C: mUC previously treated with anti-PD-(L)1 |
Enfortumab
vedotin Part A: dose escalation Part B/C: dose expansion |
112 | 43 | 16.4 | 5.4 | 12.3 | 7.4 | Part B
completed accrual Part A/C results published |
|
| EV-201
NCT03219333 |
II | Cohort 1: LA/mUC
previously treated with anti-PD-(L)1 and PBC Cohort 2: LA/mUC previously treated with anti-PD-(L)1 and cisplatin- ineligible |
Enfortumab
vedotin |
125 | 44 | 72 | 10.2 | 5.8 | 11.7 | 7.6 | Cohort
1 results published Cohort 2 recruiting |
| EV-103
NCT03288545 |
Cohort A: 1L mUC,
cisplatin-ineligible |
Cohort A:
Enfortumab vedotin + pembrolizumab |
45 | 73.3 | 93.3 | 11.5 | 12.3 | NR | Cohort
A results presented, additional cohorts recruiting |
||
| NCT01631552 | I/II | LA/mUC with
progression after at least 1 prior therapy |
Sacituzumab
govitecan |
45 | 31 | 7.3 | 18.9 | 12.6 | Results
presented |
||
| TROPHY-U-01
NCT03547973 |
II | Cohort 1: LA/mUC
with progression after PBC and anti- PD-(L)1 Cohort 2: LA/mUC with progression after anti-PD-(L)1 and platinum- ineligible Cohort 3: LA/mUC with progression after PBC |
Cohort 1+2:
Sacituzumab govitecan Cohort 3: sacituzumab govitecan + pembrolizumab |
35 | 29 | 4.1 | Cohort 1
preliminary results presented Cohort 2+3 recruiting |
1L, first line; BSC, best supportive care; DCR, disease control rate; HR, hazard ratio; IC2/3, PD-L1 expression on at least 5% of tumor-infiltrating immune cells; LA, locally advanced; mDOR, median duration of response; mOS, median overall survival; mPFS, median progression-free survival; mUC, metastatic urothelial carcinoma; NR, not reached; ORR, overall response rate; PBC, platinum-based chemotherapy; SD, stable disease.