Table 1.
NCT Identifier, Trial Name | Agent | Target | Phase | Population | Response, OR% (CR%) | OS (mo) | AEs | PD-L1 + definition | Refs. |
---|---|---|---|---|---|---|---|---|---|
JAVELIN Solid Tumor, NCT01772004 | Avelumab | PD-L1 | Ib | Multiple tumor types, UC = 44. Metastatic, postplatinum |
18.2 (4.5), PD-L1 + : 50 | 12mo OS: 50.9% | Gr ≥ 3 trAE: 11 | PD-L1+ ≥5% IC | [85] |
NCT02108652 IMvigor 210 | Atezolizumab | PD-L1 | II | C 1: first-line cisineligible (n = 119) | C 1: 24 (7) | C 1: 14.8 | Cohort 1: Gr 3-4 trAE: 15 |
PD-L1 IC0: <1% IC | C 1: [86] |
C 2: Postplatinum (n = 311) | PD-L1+: 25 (6) C 2: 15 (5) PD-L1+: 18 (6) |
C 2: 7.9 | Gr 5 trAE: 1 Cohort 2: G3-4 trAE: 16 |
PD-L1 IC1: ≥1 ≤ 5% IC PD-L1 IC2/3: ≥5% IC |
C 2: [28] | ||||
NCT01928394 | Nivolumab | PD-1 | I/II | Multiple tumor types (UC = 78) | 24.4 (6.4) | 9.7 | G3-4 trAE: 20.5 | PL-L1 + if expression ≥ 1% TC | [34, 87] |
CheckMate 032 | Nivolumab + Ipiliumab (3/1 and 1/3) | CTLA-4 | Metastatic, postplatinum | G5 trAE: 2.6 | |||||
N3/I1 (n = 104) | 26.0 | NR | 31.7 | ||||||
N1/I3 (n = 26) | 38.5 | NR | 30.8 | ||||||
NCT02387996 CheckMate 275 |
Nivolumab | PD-1 | II | Postplatinum, metastatic or locally advanced UC (n = 265) | 19.6 (2) PD-L1 ≥ 5%: 28.4 PD-L1 ≥ 1%: 23.8 PD-L1-: 16.1 |
8.7 | G3-4 trAE: 18 G5 trAE: 1.1 |
PL-L1 + if expression ≥1% TC (also reported outcomes for PD-L1 ≥ 5%) | [88] |
NCT01693562 | Durvalumab | PD-L1 | I/II | Multiple tumor types (UC = 61) Metastatic (57 > first line) |
31.0% PD-L1 + : 46.4 PD-L1-: 0 |
NR | G3 trAE: 4.9 G4-5 trAE: 0 |
PD-L1+ if ≥ 25% of TC or IC | [89] |
NCT01848834 KEYNOTE-012 |
Pembrolizumab | PD-1 | I | Multiple tumor types (UC = 33) Metastatic, 76% > first line |
27.6 (10.3) PD-L1 + : 29-33 PD-L1-: 0-9 |
12.7 | G3 trAE: 9.1 G4-5 tRAE: 0 |
PD-L1+ if staining in stroma or ≥ 1% TC | [90] |
NCT02335424 KEYNOTE-052 |
Pembrolizumab | PD-1 | II | First-line cisplatin-ineligible metastatic or locally advanced (n = 349) | 24.0 (6.0) PD-L1 ≥ 10%: 36.7 (13.3) PD-L1 ≥ 1%: 25.4 (6.3) |
NR | Gr ≥ 3 trAE: 16% | PD-L1 + if: ≥ 10% combined TC and IC (also reported response if ≥ 1%) | [91] |
NCT02256436 KEYNOTE-045 |
Pembrolizumab | PD-1 | III | Second-line postplatinum pembrolizumab (n = 270) vs. paclitaxel, docetaxel, or vinflunine (n = 272) | 21.1 (7.0) vs. 11.4 (3.3) | 10.3 vs. 7.4 (HR = 0.73, P = 0.002) | Gr ≥ 3 trAE: 15 vs. 49 | PD-L1 + if: ≥ 10% combined TC and IC | [29] |
BSC = best supportive care; C1 = cohort 1; C2 = cohort 2; Chemo = chemotherapy; Cis = cisplatin; CR = complete response; DFS = disease free survival; GC = gemcitabine þ cisplatin; GCa = gemcitabine þ carboplatin; MIBC = muscle-invasive bladder cancer; IC = immune cells; NR = not reported; OR = objective response; OS = overall survival; PC = placebo-controlled; PFS = progression free survival; Ref = reference; RPIII = randomized, phase III trial; SD = stable disease; TC = tumor cells; trAE = treatment-related adverse events; UC = urothelial carcinoma.