Table 3.
Ongoing clinical trials of molecularly targeted agents in patients with metastatic urothelial cancer
| Drug | Clinical trial, phase | Treatment arm(s) | Main inclusion criteria | |
|---|---|---|---|---|
| FGFR inhibitor | ||||
| Erdafitinib | THOR (NCT03390504), phase III | Erdafitinib vs. chemotherapy or pembrolizumab | Platinum-treated with/without ICI-treated mUC with FGFR mutation or fusions/translocations | |
| Pemigatinib | FIGHT-201 (NCT02872714), phase II | Pemigatinib | Platinum-treated or unfit mUC with FGFR3 mutations/fusions or other FGF/FGFR alterations | |
| Debio1347 | FUZE (NCT03834220), phase II basket trial | Debio1347 | Treatment refractory solid tumors harboring FGFR1–3 fusions/translocations | |
| FGFR inhibitor in combination with ICI | ||||
| Rogaratinib/atezolizumab | FORT-2 (NCT03473756), phase Ib/II | Rogaratinib + atezolizumab vs. placebo + atezolizumab | Treatment-naïve cisplatin-unfit mUC with high FGFR1 or 3 mRNA expression | |
| Pemigatinib/pembrolizumab | FIGHT-205 (NCT04003610), phase II | Pemigatinib vs. pemigatinib + pembrolizumab vs. standard of care (chemotherapy or pembrolizumab) | Treatment-naïve cisplatin-unfit mUC with FGFR3 mutation/fusion | |
| Erdafitinib/cetrelimab | NORSE (NCT03473743), phase Ib/II | Erdafitinib vs. erdafitinib + cetrelimab | Treatment-naïve cisplatin-unfit mUC with FGFR3 mutation/fusion | |
| Derazantinib/atezolizumab | FIDES-02 (NCT04045613), phase II | Derazantinib vs. derazantinib + atezolizumab | Treatment-naïve mUC with FGFR alteration | |
| ErbB family inhibitor | ||||
| Afatinib | LUX-Bladder1 (NCT02780687), phase II | Afatinib | Platinum-treated or unfit mUC with HER2 or HER3 mutation or HER2 amplification (cohort A); EGFR amplification (cohort B) | |
| Pertuzumab/trastuzumab | MyPathway (NCT02091141), phase II basket | Pertuzumab + trastzumab | Treatment refractory solid tumors with HER2 amplification (by NGS, FISH or CISH) and/or IHC3+and/or HER2 actionable mutation | |
| VEGF inhibitor in combination with ICIs | ||||
| Lenvatinib/pembrolizumab | LEAP-011 (NCT03898180), phase III | Pembrolizumab + lenvatinib vs. pembrolizumab + placebo | Treatment-naïve cisplatin-unfit PD-L1(+) or platinum-unfit mUC | |
| Bevacizumab/atezolizumab | HCRN GU15-215 (NCT03272217), phase II | Bevacizumab + atezolizumab | Treatment-naïve cisplatin-unfit mUC | |
| Cabozantinib/pembrolizumab | PemCab (NCT03534804), phase II | Cabozantinib + pembrolizumab | Treatment-naïve cisplatin-unfit mUC | |
| Cabozantinib/durvalumab | ARCADIA (NCT03824691), phase II | Cabozantinib + durvalumab | Platinum-treated mUC | |
FGFR, fibroblast growth factor receptor; ICI, immune checkpoint inhibitor; mUC, metastatic urothelial cancer; HER, human epidermal growth factor receptor; EGFR, epidermal growth factor receptor; NGS, next generation sequencing; FISH, fluorescent in situ hybridization; CISH, chromogenic in situ hydridization; IHC, immunohistochemical staining; VEGF, vascular endothelial growth factor; PD-L1, programmed death ligand-1.