Summary of FGFR inhibitors currently under investigation in clinical trials
| Inhibitor (drug ID) | Targets | IC50 (nM) | Clinical trials | Cancer types | Results |
|---|---|---|---|---|---|
| Non-selective inhibitors | |||||
| Dovitinib (TKI258) | FGFR1/2/3; KIT; VEGFR | FLT3: 1, KIT: 2, FGFR1: 8, VEGFR3: 8, FGFR3: 9, VEGFR1: 10 | Phase II NCT01861197 | FGFR1-amplified squamous NSCLC | ORR: 11.5%; DCR: 50%; mPFS: 2.9 m; mOS: 5.0 m |
| Phase II NCT01379534 | FGFR2-mutated or WT EC | ORR: 4.5% vs. 16.5%; DCR: 63.6% vs. 51.6%; PFS: 4.1 m vs. 2.7 m; 18-week PFS rate: 31.8% vs. 29%; mOS: 20.2 m vs. 9.3 m (FGFR2 mutation vs. WT) | |||
| Phase III NCT01223027 | Metastatic renal cell cancer | mPFS: 3.7 m vs. 3.6 m (Dovitinib vs. Sorafenib) | |||
| Derazantinib (ARQ-087) | FGFR1/2/3; KIT; VEGFR; PDGFRβ | FGFR2: 1.8, FGFR1: 4.5, FGFR3: 4.5, FGFR4: 34, RET: 3, DDR2: 3.6, VEGFR1: 11, KIT: 8.2 | Phase I/II NCT01752920 | FGFR aberrant advanced solid tumors | RP2D: 300 mg QD; ORR: 20.7%; DCR: 82.8%; mPFS: 5.7 m (all pts); mPFS: 7.95 m (FGFR2 fusion-positive pts) |
| ODM-203 | Pan-FGFR; VEGFR1/2/3 | FGFR1: 11, FGFR2: 16, FGFR3: 6, FGFR4: 35, VEGFR1: 26 | Phase I/IIa NCT02264418 | Advanced or metastatic solid tumors | ORR: 9.2%; mPFS: 16.1 and 12.4 weeks for aberrant or non-aberrant FGFR |
| LY2874455 | Pan-FGFR; VEGFR2 | FGFR1: 2.8, FGFR2: 2.6, FGFR3: 6.4, FGFR4: 6, VEGFR2: 7 | Phase I NCT01212107 | Advanced or metastatic solid tumors | RP2D: 16 mg BID |
| Selective inhibitors | |||||
| Erdafitinib (JNJ-42756493) | Pan-FGFR | FGFR1: 1.2, FGFR2: 2.5, FGFR3: 3.0, FGFR4: 5.7 | FDA approved Phase II NCT02365597 | FGFR2/FGFR3 aberrant UC | ORR: 40%; mPFS: 5.5 m; mOS: 13.8 m |
| Phase I/IIa NCT02421185 | FGF19-amplified HCC | ORR: 4.8%; DCR: 35.7% vs. 9.1%; m PFS: 1.58 m vs. 1.31 m (FGF19 amplifcation vs. no-FGF19 amplifcation) | |||
| Pemigatinib (INCB054828) | Pan-FGFR | FGFR1: 0.4, FGFR2: 0.5, FGFR3: 1.0, FGFR4: 30 | FDA approved Phase II NCT02924376 | FGFR2 fusions or rearrangement in CCA | ORR: 35.5%; m PFS: 6.9 m; mOS: 21.1 m; mDOR: 7.5 m; DCR: 82.0% |
| Infigratinib (BGJ398) | Pan-FGFR | FGFR1: 0.9, FGFR2: 1.4, FGFR3: 1.0, FGFR4: 60 | FDA approved Phase II NCT02150967 | FGFRs aberrant CCA | ORR: 14.8%; DCR: 75.4%; m PFS: 5.8 m |
| Phase II NCT02160041 | FGFRs aberrant malignancies | CBR: 15%; ORR: 7.5%; mPFS: 1.8 m; OS: 6.2 m | |||
| Futibatinib (TAS-120) | Pan-FGFR | FGFR1: 3.9, FGFR2: 1.3, FGFR3: 1.6, FGFR4: 8.3 | FDA approved Phase II NCT02052778 | FGFR2 fusions/rearrangement in iCCA | ORR: 42%; mPFS: 9.0 m; OS: 27.1 m |
| Gunagratinib (ICP-192) | Pan-FGFR | FGFR1: 1.4, FGFR2: 1.5, FGFR3: 2.6, FGFR4: 3.5 | Phase I/IIa NCT03758664 | FGFR2 translocation/fusion in CCA | CR: 8.4%, PR: 25.0%, SD: 58.3% (12 pts) |
| ASP5878 | Pan-FGFR | FGFR1: 0.5, FGFR2: 0.6, FGFR3: 0.7, FGFR4: 3.5 | Phase I NCT02038673 | FGFRs aberrant UC,HCC or squamous NSCLC | NA |
| Rogaratinib (BAY-1163877) | Pan-FGFR | FGFR1: 1.8, FGFR2: < 1, FGFR3: 9.2, FGFR4: 1.2 | Phase II/III NCT03410693 | FGFR-positive UC processed with prior platinum-containing chemotherapy | ORR: 20.7% vs. 19.3%; mPFS: 8.3 m vs. 9.8 m (rogaratinib vs. chemotherapy) |
| AZD4547 | FGFR1/2/3 | FGFR1: 0.2, FGFR2: 2.5, FGFR3: 1.8 | Phase II NCT02465060 | FGFR1/2/3 aberrant tumuors | ORR: 8%, mPFS: 3.4 m, 6-month PFS rate: 15%; (For FGFR fusions patients, ORR: 22%, 6-month PFS: 56%) |
| Phase II NCT01457846 | FGFR2-amplified or polysomic GC | mPFS: 1.8 m vs. 3.5 m (AZD4547 vs. Paclitaxel) | |||
| CH5183284 (Debio-1347) | FGFR1/2/3 | FGFR1: 9.3, FGFR2: 7.6, FGFR3: 22, FGFR4: 290 | Phase I NCT01948297 | FGFR1-3 altered solid malignancies | PR: 10%, SD: 27.5%, PD: 60% (58 pts) |
| Phase II NCT03834220 | FGFR 1/2/3 gene fusion or rearrangement in solid tumors | NA | |||
| E7090 | FGFR1/2/3 | FGFR2: 1.2 | Phase I NCT02275910 | Advanced solid tumors regardless of FGFR alteration | PR: 4%, SD: 29%, PD: 58% (24 pts) |
| Phase II NCT04238715 | FGFR2 gene fusions in CCA | NA | |||
| HMPL-453 | FGFR1/2/3 | FGFR1: 6, FGFR2: 4, FGFR3: 6 | Phase II NCT04353375 | FGFR2 fusions in advanced bile duct cancer | NA |
| Fisogatinib (BLU-554) | FGFR4 | FGFR4: 5 | Phase I NCT02508467 | FGF19 positive advanced HCC | ORR: 17% vs. 0%; mPFS: 3.3 m vs. 2.3 m (FGF19-positive vs. FGF19-negative) |
| Roblitinib (FGF401) | FGFR4 | FGFR4: 1.9 | Phase I/II NCT02325739 | FGF19 positive advanced HCC | RP2D: 120 mg QD; ORR: 8%, SD: 53%, mPFS: 4.1 m |
| H3B-6527 | FGFR4 | FGFR4: < 1.2 | Phase I NCT02834780 | Advanced HCC or iCCA | NA |
| Monoclonal antibodies and ligand traps | |||||
| Vofatamab | FGFR3 | NA | Phase Ib/II NCT02401542 | Vofatamab ± Docetaxel in UC | ORR: 11% (7/61) |
| Phase Ib/II NCT03123055 | Vofatamab + Pembrolizumab in UC | ORR: 11% (7/61) | |||
| Bemarituzumab (FPA114) | FGFR2b | NA | Phase II NCT0369452 | FGFR2b overexpressed and/or FGFR amplified G/GEJC | mPFS: 9.5 m vs. 7.4 m; mOS: not reached vs. 12.9 m (mFOLFOX6 + bemarituzumab vs. mFOLFOX6 + placebo) |
| FP-1039 | FGF2 trap | FGFR2: 0.023 μg/mL | Phase I NCT01868022 | FGFR genetically aberrant solid malignancies | DLT: 0.75 mg/kg (urticaria), 1 mg/kg (intestinal perforation and neutropenia), and 16 mg/kg (muscular weakness) |
NA, not available; NSCLC, non-small cell lung cancer; WT, wild type; EC, endometrial cancer; HCC, hepatocellular carcinoma; iCCA, intrahepatic cholangiocarcinoma; UC, urothelial carcinoma; GC, gastric cancer; G/GEJC, gastric/gastroesophageal junction cancer; ORR, objective response rate; DCR, disease control rate; mPFS, median progression-free survival; mOS, median overall survival; RP2D, recommended phase II dose; QD, once daily; BID, twice daily.