Table 1 Emerging targets with clinical significance in urothelial carcinoma
Molecular target | Class | Trial | Disease setting | Agent | Experimental treatment | Study phase | Estimated completion |
|---|---|---|---|---|---|---|---|
PD-1/PD-L1 | CPI | NCT02807636 (IMvigor130) | Untreated mUC | Atezolizumab | Atezolizumab + (Carboplatin) (Gemcitabine) (Cisplatin) | Phase III | November 2020 |
NCT02853305 (Keynote-361) | Untreated mUC | Pembrolizumab | Pembrolizumab + (Cisplatin) (Carboplatin) (Gemcitabine) | Phase III | May 2020 | ||
CTLA-4 | NCT02516241 (DANUBE) | Untreated mUC | Tremelimumab | Durvalumab + tremelimumab or durvalumab monotherapy | Phase III | September 2019 | |
CD122 | Cytokine Modulation | NCT02983045 (PIVOT-2) | Advanced tumors (mUC) | NKTR-214 | NKTR-214 + nivolumab or NKTR-214 + nivolumab + ipilimumab | Phase I/II | June 2021 |
NCT03785925 (Pivot-10) | Cisplatin-ineligible, mUC patients with low PD-L1 expression | NKTR-214 | NKTR-214 + nivolumab | Phase III | May 2022 | ||
NCT03138889 (PROPEL) | Advanced tumors (mUC) | NKTR-214 | NKTR-214 + pembrolizumab or NKTR-214 + atezolizumab | Phase I | May 2020 | ||
IL-7 | NCT03513952 | Advanced, inoperable or mUC | CYT107 | CYT107 + atezolizumab | Phase I | December 2020 | |
TGFβ + PD-1 | NCT02517398 | Advanced tumors (mUC) | MSB0011359C (M7824) | MSB0011359C (M7824) | Phase I | August 2020 | |
CD137/4-1BB | NCT02845323 | Cisplatin-ineligible MIBC | Urelumab | Urelumab + nivolumab or nivolumab monotherapy | Phase II | January 2020 | |
OX40 | NCT02554812 (JAVELIN Medley) | Advanced tumors (mUC) | PF-04518600 | Avelumab Utomilumab PF-04518600 PD 0360324 | Phase II | December 2020 | |
NCT03217747 | Advanced tumors (UC) | PF-04518600 | Avelumab UtomilumabPF-04518600 Radiation Cisplatin | Phase I/II | August 2023 | ||
IDO | T Cell Metabolism | NCT03361865 (Keynote-672) (ECHO307) | Cisplatin-ineligible UC | Epacadostat | Epacadostat + pembrolizumab | Phase III | September 2020 |
NCT03374488 (Keynote-698) | Cisplatin-ineligible mUC | Epacadostat | Epacadostat + pembrolizumab | Phase III | August 2020 | ||
VEGF | TKI | NCT03133390 | Cisplatin-ineligible mUC | Bevacizumab | Bevacizumab + atezolizumab | Phase II | January 2020 |
NCT03272217 | Cisplatin-ineligible untreated mUC | Bevacizumab | Bevacizumab + atezolizumab | Phase II | April 2021 | ||
cMET/VEGF | NCT02717156 | Untreated mUC | EphB4-HSA | EphB4-HAS + pembrolizumab | Phase II | November 2020 | |
NCT03534804 (PemCab) | Cisplatin-ineligible mUC | Cabozantinib | Cabozantinib + pembrolizumab | Phase II | September 2023 | ||
NCT03170960 | Advanced tumors (UC) | Cabozantinib | Cabozantinib + atezolizumab | Phase I/II | December 2020 | ||
FGFR | NCT02546661 (BISCAY) | Previously-treated MIBC | AZD4547 MEDI4736 Olaparib AZD1775 Vistusertib AZD9150 Selumetinib | Phase Ib | March 2020 | ||
NCT03123055 (FIERCE-22) | mUC | Vofatamab | Vofatamab + pembrolizumab | Phase I/II | September 2022 | ||
NCT03473756 (FORT-2) | FGFR-positive mUC | Rogaratinib | Rogaratinib + atezolizumab | Phase Ib/II | July 2022 | ||
Nectin-4 | ADC | NCT03288545 (EV-103) | mUC | Enfortumab Vedotin | Enfortumab vedotin + pembrolizumab | Phase I | September 2024 |
NCT03219333 (EV-201) | mUC previously-treated with CPI | Enfortumab Vedotin | Enfortumab vedotin | Phase II | May 2025 | ||
NCT02091999 | Nectin-4-positive mUC | Enfortumab Vedotin | Enfortumab vedotin | Phase I | December 2020 | ||
NCT03474107 (EV-301) | Previously-treated mUC | Enfortumab Vedotin | Enfortumab vedotin | Phase III | September 2021 | ||
HER-2 | NCT03523572 | mUC | Trastuzumab Deruxtecan (DS-8201a) | Trastuzumab Deruxtecan (DS-8201a) | Phase I/II | September 2020 | |