Table 2.
Summary of ongoing clinical trials with FGFR inhibitors as monotherapy or in combination with other agents in urothelial cancer
| Study, NCT identifier | Agent(s) | Study design | Estimated sample | FGFR genetic aberrations | Study cohort | Primary endpoint(s) |
|---|---|---|---|---|---|---|
| NCT04045613, FIDES‐02 | Derazantinib monotherapy or in combination with atezolizumab | Phase Ib/II, open label | 303 | Required, FGFR 1–3 mutations per fusion | Metastatic urothelial cancer, cisplatin ineligible | RP2D of derazantinib with atezolizumab; ORR based on RECIST 1.1 |
| NCT03914794 | Pemigatinib | Phase II, open label, window of opportunity study | 43 | Not required | Low‐ or intermediate‐risk NMIBC tumors prior to TURBT | Complete response on pathology |
| NCT02872714, FIGHT‐201 | Pemigatinib | Phase II, open label | 240 | Required | Metastatic urothelial cancer in first‐ or second‐line therapy | ORR in patients with FGFR3 mutations based on RECIST 1.1 |
| NCT04003610, FIGHT‐205 | Pemigatinib + pembrolizumab vs. pemigatinib vs. standard of care (chemotherapy or pembrolizumab) | Phase II, open‐label, randomized, multicenter | 372 | Required, FGFR3 mutation or rearrangement | First‐line, metastatic or unresectable urothelial carcinoma in cisplatin‐ineligible patients | PFS |
| NCT03473743 | Erdafitinib vs. erdafitinib + cetrelimab (anti‐PD‐1 monoclonal antibody) | Phase Ib/II, randomized, open label | 150 | Required | First‐line metastatic urothelial carcinoma, cisplatin ineligible | DLTs, overall response rate by RECIST 1.1 |
| NCT03390504, THOR study | Erdafitinib vs. chemotherapy (docetaxel or vinflunine) vs. pembrolizumab | Phase III, open label, randomized | 631 | Required | Metastatic urothelial carcinoma with disease progression after 1 or 2 prior treatments | OS |
| NCT02052778 | TAS‐120 | Phase I/II, single arm, open label, multicohort | 371 | Required, advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations | Patients with solid tumor including a cohort of advanced UC | ORR by RECIST 1.1 |
| NCT03834220, FUZE study | Debio 1347 | Phase II, single arm, open label Basket study | 125 | FGFR 1–3 fusion | Solid tumor FGFR alterations | ORR |
| NCT04040725, (BLASST)‐3 | Rogaratinib | Phase II, open label | 33 | Required, FGFR1 or FGFR3 gene overexpression | High‐risk NMIBC unresponsive to BCG | Complete response on TURBT |
| NCT03410693, FORT‐1 | Rogaratinib vs. chemotherapy (docetaxel, paclitaxel or vinflunine) | Phase II/III, randomized, open label | 175 | FGFR1 or 3 gene alterations | Metastatic urothelial carcinoma, received prior platinum‐containing chemotherapy | OS |
| NCT03473756, FORT‐2 | Rogaratinib + atezolizumab vs. placebo + atezolizumab | Phase Ib/II, randomized, blinded | 210 | High FGFR1 or 3 mRNA expression levels | Treatment naïve locally advanced or metastatic urothelial cancer | DLTs, AEs, and PFS |
| NCT04197986, PROOF 302 | Infigratinib vs. placebo | Phase III, randomized, blinded | 218 | FGFR 3 genetic alterations | Adjuvant therapy after definitive surgery for invasive urothelial cancer | DFS |
| NCT04228042 | Infigratinib | Phase I/II | 20 | With and without FGFR3 alterations | Prior to surgery for UTUC | Safety and ORR |
Abbreviations: AE, adverse event; DLT, dose limiting toxicity; FGFR, fibroblast growth factor receptor; NMIBC, non‐muscle invasive bladder cancer; ORR, overall response rate; OS, overall survival; PFS, progression‐free survival; RP2D, recommended phase 2 dose; TURBT, transurethral resection of bladder tumor; UC, urothelial cancer; UTUC, upper tract urothelial cancer.