Table 2.
Ongoing clinical trials of anti PD-L1 and anti PD-1 immune checkpoint inhibitors in metastatic urothelial cancer.
| Study | Phase | Regimen | Primary endpoints | Planned number of pts or pts enrolled | Status | |
|---|---|---|---|---|---|---|
| Atezolizumab | NCT02302807 (IMVigor 211) | III | Atz 1200 mg IV d1 q3w versus CT (Vnf 320 mg/m2 or Txl 175 mg/m2, or Txt 75 mg/m2) IV d1 q3w | OS | 932 | Active, not recruiting |
| NCT02807636 (IMVigor 130) | III | Atz 1200 mg IV d1 + CT (Crb AUC 4.5 IV d1 + Gem 1000 mg/m2 IV d1,8 q3w) versus Placebo + CT | OS, PFS and Safety | 435 | Currently recruiting | |
| NCT02989584 | II | Atz 1200 mg IV d8 q3w + Gem 1000 mg/m2 IV d1,8 + Cis 70 mg/m2 d1 q3w (maintenance in phase II) | Safety | 30 | Currently recruiting | |
| NCT02298153 (ECHO-110) | I | Atz 1200 mg IV q3w + Epacadostat 25 mg OS BID as starting dose, followed by dose escalations. | Safety | 118 | Currently recruiting | |
| NCT02928406 | III | Atz 1200 mg IV q3w | Safety | 1000 | Active, not recruiting | |
| NCT02655822 | I | CPI-444 in 3 different schedules versus CPI-444 + Atz IV | Safety, ORR, median AUC of CPI-444 | 534 | Currently recruiting | |
| NCT02543645 | I/II | Varlilumab 0.3 or 1 or 3 mg/kg + Atz 1200 mg IV q2w | Safety, ORR | 55 | Currently recruiting | |
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| Durvalumab | NCT02516241 | III | IV Drv +/− IV Trm versus CT (platinum + Gem) | PFS, OS | 1005 | Active, not recruiting |
| NCT02546661 (Biscay) | I | (A) Drv + AZD4547 (B) Drv + olaparib (C) Drv + AZD1775 (D) Drv (E) Drv + Vistusertib |
Safety | 110 | Currently recruiting | |
| NCT02527434 | II | IV Trm versus IV Trm + IV Drv versus IV Drv | ORR | 66 | Currently recruiting | |
| NCT02643303 | I/II | IV Drv + IV Trm +/− IT/IM PolyICLC | Recommended combination dose, safety, ORR, PFS and OS | 102 | Active, not recruiting | |
| NCT02318277 | I/II | Drv IV q2w + OS INCB024360 25 mg BID followed by dose escalations. | DLT, ORR | 185 | Currently recruiting | |
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| Avelumab | NCT02603432 (JAVELIN Bladder 100) | III | Avl IV q2w + BSC versus BSC | OS | 668 | Currently recruiting |
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| Nivolumab | NCT02387996 | II | IV Niv | ORR | 242 | Active, not recruiting |
| NCT02897765 | I | Niv IV 240 mg q2w +/− NEO-PV-01 SC + Adj | Safety | 90 | Currently recruiting | |
| NCT02496208 | I | OS cabozantinib-s-malate + IV Niv +/− IV Ipi | Safety and DLT | 66 | Currently recruiting | |
| NCT01928394 (Checkmate 032) | I/II | IV Niv +/− IV Ipi (different schedules) +/− OS Cobimetinib | ORR | 1150 | Currently recruiting | |
| NCT02636036 (SPICE) | I | IV Niv + IV Enadenotucirev | MTD | 30 | Currently recruiting | |
| NCT02834013 (DART) | II | Niv IV d1,15,29 + Ipi IV d1 q6w | ORR | 334 | Active, not recruiting | |
| NCT02614456 | I | Phase 1: IFN-γ SC 50 μg/m2 d1–7 Phase 2: IFN-γ SC QD + Niv IV d1 q2w Phase 3: Niv IV d1 q3w |
Safety, DLT | 15 | Currently recruiting | |
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| Pembrolizumab | NCT02717156 | II | Pmb IV d1 + EphB4-HSA IV d1,8,15 q3w | Safety | 60 | Active, not recruiting |
| NCT02925533 | I | IV B-701 + IV Pmb q3w | Safety | 12 | Currently recruiting | |
| NCT02560636 (PLUMMB) | I | IV Pmb + RT | MTD, Safety | 34 | Currently recruiting | |
| NCT02351739 (Keynote 143) | II | IV Pmb +/− ACP-196 | ORR | 75 | Active, not recruiting | |
| NCT02500121 | II | Pmb 200 mg IV d1 q3w versus placebo | 6 months PFS | 200 | Currently recruiting | |
| NCT02853305 (Keynote 361) | III | Pmb 200 mg IV d1 q3w +/− CT versus CT (platinum + Gem) | PFS, OS | 990 | Currently recruiting | |
| NCT02619253 | I/II | Pmb 200 mg IV d1 q3w + Vorinostat OS d1–14 q3w | Safety | 42 | Currently recruiting | |
| NCT02826564 | I | Stereotactic body radiotherapy prior to or concurrent with IV Pmb | Safety, selection of the sequence arm with a DLT < 20% | 20 | Currently recruiting | |
| NCT02880345 (Radvax) | Pilot | IV Pmb + hypofractionated RT (2 different regimens) | Safety | 14 | Active, not recruiting | |
| NCT02437370 | I | IV Pmb + IV Txt versus IV Pmb versus IV Gem | MTD | 38 | Currently recruiting | |
| NCT02043665 (Keynote 200) | I | (A) CVA21 (B) CVA21 + Pmb |
ORR | 60 | Currently recruiting | |
| NCT02581982 | II | Pmb 200 mg IV d1 + Txl IV d1,8 q3w | ORR | 27 | Currently recruiting | |
| NCT01174121 | II | Cyclophosphamide and fludarabine + Pmb + young TIL | Rate of tumor regression | 290 | Currently recruiting | |
| NCT03006887 | I | Pmb 200 mg IV d1 + Lenvatinib OS 20 mg QD q3w | Safety, DLT | 10 | Active, not recruiting | |
| NCT02501096 | I/II | Pmb 200 mg IV d1 + Lenvatinib OS QD q3w | MTD, ORR, DLT | 250 | Currently recruiting | |
| NCT02346955 (MK-6018-001) | I | Multidose escalation of CM-24 +/− Pmb 200 mg IV | Safety, DLT | 196 | Currently recruiting | |
| NCT02452424 | I/II | Dose escalation of OS PLX3397 + Pmb 200 mg IV | Safety | 400 | Currently recruiting | |
| NCT02432963 | I | IV Pmb + SC MVA-p53 Vaccine | Tolerability | 19 | Currently recruiting | |
| NCT02393248 | I/II | Phase 1: dose escalation/expansion of INCB054828 Phase 2: INCB054828 + Pmb/CT (Txt or Cis + Gem) |
MTD, pharmacodynamics | 150 | Currently recruiting | |
| NCT02443324 | I | IV Pmb + Ramucirumab IV d1 q3w | DLT | 155 | Currently recruiting | |
| NCT02856425 | I | IV Pmb + OS Nintedanib | MTD | 18 | Currently recruiting | |
Atz: atezolizumab; Avl: avelumab; Cis: cisplatin; Drv: durvalumab; Gem: gemcitabine Ipi: ipilimumab; Trm: tremelimumab; Txl: taxol; Txt: taxotere; Niv: nivolumab; Pmb: pembrolizumab.