Table 5.
Clinical trials of tyrosine kinase inhibitors in combination with immune checkpoint inhibitors for metastatic urothelial carcinoma.
| Regimen | Drug Classes | Inclusion Criteria | Trial | Phase | Status (March 2023) | Identifier | ORR | mPFS (Months) |
mOS (Months) |
|---|---|---|---|---|---|---|---|---|---|
| Erdafitinib +/− cetrelimab +/− platinum chemo | FGFRi +/− anti-PD1 +/− chemo | mUC with FGFR2/3 alterationPhase 2: 1L cisplatin-ineligible mUC | NORSE | 1b/2 | Active, not recruiting | NCT03473743 | 54.5% | 10.97 | NA |
| Futibatinib + pembrolizumab | FGFRi + anti-PD1 | Platinum-ineligible mUC | 2 | Recruiting | NCT04601857 | NA | NA | NA | |
| Rogaratinib + atezolizumab vs. atezolizumab | FGFRi + anti-PDL1 vs. anti-PDL1 | 1L mUC cisplatin-ineligible, FGFR1/3 (+) by RNAscope | FORT-2 | 1b/2 | Active, not recruiting | NCT03473756 | 54% | NA | NA |
| Derazantinib +/− atezolizumab | FGFR/CSF1R inhibitor +/− anti-PDL1 | 2L+ mUC, 1L cisplatin-ineligible mUC | FIDES-02 | 1b/2 | Completed | NCT04045613 | NA | NA | NA |
| LOXO-435 +/− pembrolizumab | FGFR3i +/− anti-PD1 | FGFR3-altered advanced solid tumors including mUC | 1 | Recruiting | NCT05614739 | NA | NA | NA | |
| Pemigatinib +/− pembrolizumab vs. gemcitabine + carboplatin | FGFRi +/− anti-PD1 vs. chemo | 1L cisplatin-ineligible mUC with an FGFR3 mutation or rearrangement | FIGHT-205 | 2 | Terminated | NCT04003610 | NA | NA | NA |
| Cabozantinib + nivolumab +/− ipilimumab | Multi-TKI + anti-PD1 +/− anti-CTLA4 | Metastatic GU cancers including mUC | 1 | Active, not recruiting | NCT02496208 | 38.5%, 16.0% | 12.8 | 25.4 | |
| Cabozantinib + nivolumab + ipilimumab | Multi-TKI + anti-PD1 + anti-CTLA4 | Rare GU tumors, metastatic bladder cancer histologic variants | ICONIC | 2 | Recruiting | NCT03866382 | NA | NA | NA |
| Cabozantinib + durvalumab | Multi-TKI + anti-PDL1 | mUC and non-UC histologies | ARCADIA | 2 | Unknown | NCT03824691 | 39.7% | 7.6 | 11.6 |
| Cabozantinib + pembrolizumab | Multi-TKI + anti-PD1 | 1L cisplatin-ineligible mUC | PemCab | 2 | Active, not recruiting | NCT03534804 | NA | NA | NA |
| Lenvatinib + pembrolizumab vs. placebo + pembrolizumab | Multi-TKI + anti-PD1 | 1L cisplatin-ineligible PD-L1 (-) or platinum- ineligible mUC | LEAP-011 | 3 | Active, not recruiting | NCT03898180 | NA | HR 0.91 (0.71–1.16) | HR 1.25 (0.94–1.67) |
| Sitravatinib + nivolumab | Multi-TKI + anti-PD1 | 8 cohorts of mUC | 2 | Terminated | NCT03606174 | 0–33% | 3.5–7.8 | NA | |
| Famitinib + camrelizumab | Multi-TKI + anti-PD1 | Advanced GU and gynecologic cancers | 2 | Recruiting | NCT03827837 | 30.6% | 4.1 | 12.9 | |
| XL092 +/− nivolumab +/− either ipilimumab or relatlimab | Multi-TKI +/− anti-PD1 +/− anti-CTLA5 or anti-LAG3 | Advanced solid tumors including mUC | STELLAR-002 | 1b | Recruiting | NCT05176483 | NA | NA | NA |
Abbreviations: FGFRi = fibroblast growth factor receptor inhibitor; mUC = metastatic urothelial carcinoma; ORR = objective response rate; mPFS = median progression-free survival; mOS = median overall survival; 1L = first line; 2L+ = second line or beyond; NA = not available; HR = hazard ratio.