From: FGFR-TKI resistance in cancer: current status and perspectives
Drugs | Company | Targets | Approved/clinical trials | Patients and clinical results |
---|---|---|---|---|
Erdafitinib (JNJ-42756493) | Janssen | Pan-FGFR | FDA approved Phase II NCT02365597 | Advanced or Metastatic urothelial carcinoma with FGFR2/FGFR3 genetic alterations and had a history of disease progression within 12Â months of neoadjuvant or adjuvant platinum-containing chemotherapy. Results: ORR: 40%; median PFS: 5.5Â months; median OS: 13.8Â months |
Phase I/IIa NCT02421185 | Advanced hepatocellular carcinoma with FGF19 amplification. Results: ORR: 4.8%; DCR: 35.7% VS 9.1%; median PFS: 1.58Â months VS 1.31Â months (FGF19 amplification VS no-FGF19 amplification) | |||
Pemigatinib (INCB054828) | Incyte | Pan-FGFR | FDA approved Phase II NCT02924376 | Documented disease progression following at least one previous systemic cancer therapy, locally advanced or metastatic cholangiocarcinoma with FGFR2 gene fusion or rearrangement. Results: ORR: 35.5%; median PFS: 6.9Â months; median OS: 21.1Â months; median DOR: 7.5Â months; DCR: 82.0% |
Futibatinib (TAS-120) | Taiho Pharm | Pan-FGFR | Phase II NCT02052778 | Disease progression after ≥ 1 line of systemic therapy (gemcitabine plus platinum-based chemotherapy), advanced or metastatic unresectable intrahepatic cholangiocarcinoma with FGFR2 gene fusions or other rearrangements. Results: ORR: 34.3%; DCR: 76.1%; median DOR: 6.2 months |
CH5183284 (Debio-1347) | Debio | FGFR1/2/3 | Phase II NCT03834220 | Solid tumors harboring FGFR 1/2/3 gene fusion or rearrangement |
ASP5878 | Astellas | Pan-FGFR | Phase I NCT02038673 | Urothelial carcinoma, hepatocellular carcinoma, or squamous cell lung carcinoma with FGFRs genetic alterations |
Dovitinib (TKI258) | Novartis | FGFR1/2/3; KIT; VEGFR | Phase II NCT01861197 | Advanced squamous non-small cell lung cancer with FGFR1 amplification. Results: ORR: 11.5%; DCR: 50%; median PFS: 2.9Â months; median OS: 5.0Â months |
Phase II NCT01379534 | FGFR2 mutated or WT advanced and/or metastatic endometrial cancer. Results: ORR: 4.5% VS 16.5%; DCR: 63.6% VS 51.6%; PFS: 4.1Â months VS 2.7Â months; 18-week PFS rate: 31.8% VS 29%; median OS: 20.2Â months VS 9.3Â months (FGFR2 mutation VS FGFR2 WT) | |||
PRN1371 | Principia | Pan-FGFR | Phase I NCT02608125 | Metastatic urothelial carcinoma with FGFRs genetic alterations |
LY2874455 | Eli-Lilly | Pan-FGFR; VEGFR2 | Phase I NCT01212107 | Advanced solid-organ cancer |
Infigratinib (BGJ398) | Novartis | Pan-FGFR | Phase II NCT02150967 | Advanced or metastatic cholangiocarcinoma with FGFRs alterations whose disease progressed despite prior systemic therapy. Results: ORR: 14.8%; DCR: 75.4%; median PFS: 5.8Â months |
Phase II NCT02160041 | Solid tumor and hematologic malignancies with FGFRs genetic alterations. Results: CBR: 15%; ORR: 7.5%; median PFS: 1.8Â months; OS: 6.2Â months | |||
AZD4547 | AstraZeneca | Pan-FGFR | Phase II NCT02465060 | Advanced refractory solid tumors, lymphomas, or multiple myeloma with FGFR1/2/3 aberrations. Results: Median PFS: 3.4Â months, 6-month PFS rate: 15%; (For FGFR fusions patients, ORR: 22%, 6-month PFS: 56%) |
Derazantinib (ARQ-087) | Basilea | Pan-FGFR; RET; DDR2; KIT;VEGFR; PDGFRβ | Phase I/II NCT01752920 | Advanced, inoperable, or metastatic solid tumors with FGFRs genetic alterations who failed to respond to standard therapy or for whom standard curative therapy does not exist. Results: ORR: 20.7%; DCR: 82.8%; median PFS: 5.7 months |
E7090 | Eisai | FGFR1/2/3 | Phase II NCT04238715 | Unresectable advanced or metastatic cholangiocarcinoma with FGFR2 gene fusions |
HMPL-453 | Chi-Med | FGFR1/2/3 | Phase II NCT04353375 | Advanced bile duct cancer with FGFR2 fusions |
Rogaratinib (BAY-1163877) | Bayer | Pan-FGFR | Phase III NCT03410693 | Advanced or metastatic urothelial carcinoma with FGFR-positive after receiving prior platinum-containing chemotherapy (Rogaratinib VS chemotherapy) |
Roblitinib (FGF401) | Novartis | FGFR4 | Phase I/II NCT02325739 | FGF19-driven hepatocellular cancer |
ODM-203 | Orion | FGFR; VEGFR1/2/3 | Phase I/IIa NCT02264418 | Advanced or metastatic solid tumors for which treatment according to the guidelines was no longer available. Results: ORR: 9.2%; median PFS: 16.1 and 12.4Â weeks for aberrant or non-aberrant FGFR |
ICP-192 | InnoCare | Pan-FGFR | Phase II NCT04492293 | Surgically unresectable or metastatic bladder urothelial cancer with FGFRs genetic aberrations |
H3B-6527 | Eisai /H3 | FGFR4 | Phase I NCT02834780 | Advanced hepatocellular carcinoma and intrahepatic cholangiocarcinoma |
Fisogatinib (BLU-554) | Blueprint | FGFR4 | Phase I NCT02508467 | FGF19 positive advanced hepatocellular carcinoma. Results: ORR: 17% VS 0%; median PFS: 3.3Â months VS 2.3Â months (FGF19-positive VS FGF19-negative) |