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. Author manuscript; available in PMC: 2023 Sep 28.
Published in final edited form as: Biochim Biophys Acta Rev Cancer. 2021 Jul 23;1876(2):188595. doi: 10.1016/j.bbcan.2021.188595

Table 1:

FGFR TKIs tested or currently in clinical trials for advanced/metastatic breast cancer.

Inhibitor Phase Description of treatment arms Primary Endpoint Main results Clinical trial identifier
Non-selective inhibitors
Dovitinib II

  • ER+/FGFR1amp (n=23)

  • ER-/FGFR1amp (n=2)

  • ER+/non-FGFR1amp (n=34)

  • ER-/non-FGFR1amp (n=22)

 ORR

  • PRnca = 15% in HR+/FGFR1amp cohort

  • FGFR1 copy number ≥6 (n=7): 20.2% reduction in tumor size

 NCT00958971
II ER+/HER2− patients.Stratification based on FGFR1, FGFR2 or FGF3 amplification and presence of visceral disease

  • Dovitinib + fulvestrant (n=47)b

  • Placebo + fulvestrant (n=50)c

  • PFS in overall population

  • PFS in subgroup with FGF pathway amplification

  • PFS: 5.5 vs 5.5 months (dovitinib vs placebo, overall population)

  • PFS: 10.9 vs 5.5 months (dovitinib vs placebo, FGF pathway-amplified subgroup)

 NCT01528345
I/II Dovitinib + aromatase inhibitors in ER+/HER2− breast cancer (n=12) CBR (at 24 weeks) N/A (study terminated) NCT01484041
Lucitanib I/IIa Advanced solid tumors:
  • Breast cancer cohort (n=19)
    • FGF aberrant (FGFR1 or FGF3/4/19 amplification, n=12)

  • MTD

  • ORR

 In FGF aberrant breast cancer cohort:

  • PR = 50% (n=6)

  • SD = 50% (n=6)

  • mPFS = 40.4 weeks

 NCT01283945
II ER+/HER2− MBC

  • FGFR1amp

  • Non-FGFR1amp, 11q13 amp

  • Non-FGFR1amp, non-11q13 amp

 ORR In FGFR1amp cohort:

  • ORR=19%

  • CBR (CR, PR and SD ≥ 24 weeks) = 41%

 NCT02053636
Selective inhibitors
AZD4547 II HER2−/FGFR1amp breast cancerd (n=8) ORR PR = 12.5% (n=1) EudraCT No. 2011-003718-18
II Advanced solid tumors with FGFR aberrations (n=48):
  • Breast cancer (n=16)
    • FGFR1amp (n=11)
    • FGFR2amp (n=2)
    • FGFR2 mut (n=3)
 ORR In Breast cancer cohort:
None of the patients reached PR or SD ≥ 6 months		 NCT02465060
AZD4547 IIa ER+/HER2− breast cancer, with FGFR1 polysomy or gene amplification

  • AZD4547 + exemestane

  • AZD4547 + fulvestrant

  • Placebo + fulvestrant

 Safety N/A (study terminated) NCT01202591
IIa ER+/HER2− MBCf

  • AZD4547 + anastrozole or letrozole

  • Safety

  • ORR (at 12 weeks)

 N/A NCT01791985
II HER2− MBC with FGFR alterationsg

  • AZD4547

  • Standard maintenance chemotherapy

 PFS N/A (not recruiting; pending results) NCT02299999
Infigratinib (NVP-BGJ398) Ib ER+/HER2−/FGFRaltered MBC

  • Infigratinib + Tamoxifen

 DLTs N/A (active recruiting) NCT04504331
Ib Advanced solid tumors with concomitant PIK3CA mutations and FGFR1–3 alterations

  • Infigratinib + BYL719

 DLTs N/A (recruitment completed) NCT01928459
Zoligratinib (Debio-1347 Ib ER+/HER2−/FGFR amplified MBC

  • Zoligratinib + fulvestrant

 MTD N/A (active, not recruiting) NCT03344536
Erdafitinib (JNJ-42756493) Ib ER+/HER2−/FGFR amplified MBCh

  • Erdafitinib + palbociclib + fulvestrant

 DLTs and MTD N/A (active, not recruiting) NCT03238196
II Advanced solid tumors or lymphomah
Subprotocol K1-K2i: patients with FGFR amplification, mutations or fusions		 ORR N/A (recruiting) NCT02465060
Futibatinib (TAS-120) II Locally advanced/MBC with FGFR1–2 amplificationh
  • FGFR2 amplified
    • ER+/HER2−j: futibatinib
    • TNBCj: futibatinib
    • ER+/HER2− or TNBCk: futibatinib
  • FGFR1 amplified
    • ER+/HER2j-: futibatinib + fulvestrant

  • ORR

  • CBR

  • 6-month PFS

 N/A (recruiting) NCT04024436
Rogaratinib (Bay 1163877) I Advanced ER+/HER2− FGFR1–3 positivel,m

  • Rogaratinib + palbociclib + fulvestrant

  • RP2D

  • Incidence of TEAEs

 N/A (recruiting) NCT04483505
Pemigatinib I/II Advanced solid tumors with FGF/FGFR alterations

  • Pemigatinib single agent

  • Pemigatinib combinationn

  • MTD

  • Pharmacodynamics (serum phosphorus levels)

 N/A (recruiting) NCT02393248

ER+: estrogen receptor positive; HER2: human epidermal growth factor receptor 2; FGFR: fibroblast growth factor receptor; FGF: fibroblast growth factor; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; MBC: metastatic breast cancer; ORR: overall response rate; PR: partial response; PFS: progression free survival; CBR: clinical benefit rate; SD: stable disease; CR: complete response; MTD: maximum tolerated dose; DLT: dose limiting toxicity; RP2D: recommended phase II dose; TEAEs: treatment emergent adverse events; N/A: not available;

a:

Partial Response not confirmed at following radiological assessment;

b:

FGF pathway amplified: NO, n=32 (68.1%); YES, n=15 (31.9%);

c:

FGF pathway amplified: NO, n=33 (66.0%); YES, n=17 (34.0%);

d:

Estrogen Receptor status not specified;

e:

Patients progressed on previous endocrine therapy;

f:

Patients not selected based on FGF/FGFR status;

g:

Patients who received 6 to 8 cycles of chemotherapy, or having received at least 4 cycles of chemotherapy definitively stopped for toxicity reasons, and who are presenting a SD or PR at randomization, as per SAFIR02_BREAST study protocol;

h:

At least one previous line of therapy in the metastatic setting;

i:

Subprotocols of “The MATCH Screening Trial”;

j:

Measurable disease;

k:

Non-measurable disease;

l:

FGFR1–3 positivity evaluated by RNA-Scopre and/or FISH. Cut-offs not available;

m:

Patients progression on combination of aromatase inhibitor plus palbociclib;

n:

Combination therapies with pemigatinib: gemcitabine + cisplatin; pembrolizumab; docetaxel; trastuzumab; INCMGA00012.