Table 2.
Ongoing clinical trials targeting genetic alterations in advanced bladder cancer (not including FGFRs).
| Drug Name | Phase | Setting | Targeted GA | Intervention | #Pts | Status | NCT # |
|---|---|---|---|---|---|---|---|
| ErbB Inhibitors | |||||||
| Ado-Trastuzumab | II | Adv/Met UC, Erbb2 GA | Erbb2 | ado-trastuzumab | 135 | Recruiting | 02675829 |
| Afatinib | II | Adv/Met UC, no standard options available | Erbb1 | afatinib | 160 | Recruiting | 02795156 * |
| II | Adv/Met UC, platinum-refractory | Erbb1 | afatinib | 95 | Recruiting | 02122172 | |
| RC48-ADC | II | Adv/Met UC, cisplatin-refractory ErbB2 overexpression | ErbB2 | RC48-ADC | 60 | Active, not recruiting | 03809013 |
| Tucatinib, Trastuzumab | II | Adv/Met UC, Erbb2 GA | Erbb2 | tucatinib + trastuzumab | 270 | Recruiting | 04579380 |
| PI3K/Akt/mTOR Pathway | |||||||
| Sapanisertib | II | Adv/Met UC, platinum-refractory, with TSC GA | mTOR | sapanisertib | 209 | Active, not recruiting | 03047213 |
|
Temsirolimus
Bevacizumab Cetuximab |
I | Adv/Met UC, relapsed after standard therapy | mTOR, EGFR, VEGF | temsirolimus + bevacizumab +/− cetuximab | 155 | Active, not recruiting | 01552434 |
| Chromatin Remodeling | |||||||
| Belinostat | I | Adv/Met UC, no standard therapy available, ARID1A lof | HDAC | tremelimumab + durvalumab + belinostat | 9 | Recruiting | 05154994 |
| Entinostat | II | MIBC, Neoadjuvant | HDAC | entinostat + pembrolizumab | 20 | Recruiting | 03978624 |
| Tazemetostat | I/II | Adv/Met UC, cisplatin-refractory | EZH2 | tazemetostat + pembrolizumab | 30 | Recruiting | 03854474 |
| Vorinostat | I/Ib | Adv/Met UC, platinum-refractory | HDAC | vorinostat + pembrolizumab | 57 | Active, not recruiting | 02619253 |
| Cell Cycle Regulation | |||||||
| Trilaciclib | II | Adv/Met UC—first line | CDK4/6 | trilaciclib + platinum chemo then trilaciclib + avelumab | 90 | Recruiting | 04887831 |
| DNA Damage Repair | |||||||
| Niraparib | I/II | Adv/Met UC, platinum-refractory | DDR, RTKs | niraparib + cabozantinib | 20 | Recruiting | 03425201 |
| Olaparib | II | Adv/Met UC, platinum, or PD1/L1 refractory | DDR | olaparib | 60 | Recruiting | 03375307 |
| II | Adv/Met UC, ARID1A mutated, ATM mutated | DDR, ATM | olaparib + AZD6738 | 68 | Recruiting | 03682289 | |
| Talazoparib | II | Adv/Met UC, s/p platinum with stable disease | DDR | talazoparib + avelumab | 50 | Recruiting | 04678362 |
| Umbrella/Basket/Multi-Arm Trials | |||||||
| BISCAY | Ib | Metastatic UC, 2nd or 3rd line | HRR, CKDN2A, RB1, MAPK, mTOR | olaparib + durvalumab AZD1775 + durvalumab selumetinib + durvalumab vistusertib + durvalumab |
156 | Active, not recruiting | 02546661 * |
| My Pathway | IIa | Adv/Met UC, Erbb1 or Erbb2 GA | Erbb1, Erbb2, BRAF | trastuzumab + pertuzumab or Erlotinib or vemurafenib + cobimetinib | 676 | Active, not recruiting | 02091141 * |
| The Match Screening Trial | II | Adv/Met UC, relapsed after standard therapy | P13K, PTEN, AKT, mTOR, BRAF, NRAS, CCND1 | copanlisib or capivasertib or ipatasertib or sapanisertib or trametinib or binimetinib or dabrafenib or palbociclib | 6452 | Recruiting | 02465060 * |
| SEASTAR | Ib/II | Adv/Met UC progressed on 1 previous therapy | DDR, VEGF, FGFRs, PDGFRs | rucaparib + lucitanib rucaparib + sacituzumab govitecan |
329 | Active, not recruiting | 03992131 |
* Trial with additional treatment arms not mentioned in the table. Abbreviations: Adv, Advanced; Met, Metastatic; TSC, Tuberous Sclerosis Complex; HRR, Homologous Recombination Repair; lof, loss of function; GA, Genetic Alteration; Pts, Patients; DDR, DNA Damage Repair; RTKs, Receptor Tyrosine Kinases; PD1/L1, Programmed Death 1/Programmed Death Ligand 1 Inhibitor; ATM, PDGR, Platelet-derived Growth Factor Receptors.