Table 1 Clinical development of FGFR-TKIs

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 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Results: ORR: 40%; median PFS: 5.5 months; median OS: 13.8 months

Phase I/IIa

NCT02421185

Advanced hepatocellular carcinoma with FGF19 amplification. Results: ORR: 4.8%; DCR: 35.7% VS 9.1%; median PFS: 1.58 months VS 1.31 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: 6.9 months; median OS: 21.1 months; median DOR: 7.5 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: 2.9 months; median OS: 5.0 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: 4.1 months VS 2.7 months; 18-week PFS rate: 31.8% VS 29%; median OS: 20.2 months VS 9.3 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: 5.8 months

Phase II

NCT02160041

Solid tumor and hematologic malignancies with FGFRs genetic alterations. Results: CBR: 15%; ORR: 7.5%; median PFS: 1.8 months; OS: 6.2 months

AZD4547

AstraZeneca

Pan-FGFR

Phase II

NCT02465060

Advanced refractory solid tumors, lymphomas, or multiple myeloma with FGFR1/2/3 aberrations. Results: Median PFS: 3.4 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 12.4 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: 3.3 months VS 2.3 months (FGF19-positive VS FGF19-negative)