151O - Preclinical characterization of alofanib, a novel allosteric FGFR2 inhibitor

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Developmental therapeutics
Topics Clinical Research
Presenter Ilya Tsimafeyeu
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors I. Tsimafeyeu1, E. Stepanova2, D. Khochenkov2, G. Murillo3, N. Lapina4, E. Gavrilova5, M. Byakhov6, S. Tjulandin7
  • 1Moscow Office, Kidney Cancer Research Bureau, 109147 - Moscow/RU
  • 2Laboratory Of Biomarkers And Tumor Angiogenesis, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU
  • 3Research Institute, Illinois Institute of Technology, 60616 - Chicago/US
  • 4Laboratory Of Toxicology And Pharmacology, Institute of Toxicology of Federal Medical-Biological Agency, 192019 - St. Petersburg/RU
  • 5Spb Office, Ruspharmtech LLC, 190121 - Saint Petersburg/RU
  • 6Department Of Chemotherapy, Moscow Clinical and Research Center, 111123 - Moscow/RU
  • 7Department Of Clinical Pharmacology And Chemotherapy, N. N. Blokhin Russian Cancer Research Center, 115478 - Moscow/RU



Alofanib (RPT835) is a novel selective allosteric inhibitor binding to the extracellular domain of FGFR2. Here, we report preclinical pharmacology and toxicity of alofanib.


To assess the efficacy of alofanib on FGF-mediated cell proliferation, SKOV3 (ovarian cancer), SUM52PE (triple negative breast cancer), HS578T (triple negative breast cancer), HUVEC (endothelial), and hFOB (osteoblast) cells were treated with serially diluted alofanib. Studies in xenograft models were performed using SKOV3, SUM52PE, HS578T, NCI-H226 (lung cancer), and HCT116 (colon cancer) cells with different levels of FGFR2 expression. Mice were randomized into treatment and vehicle groups. In ovarian cancer study, alofanib was used in combination with carboplatin/paclitaxel i.v. or orally. Three preclinical pharmacokinetic (PK) studies were conducted to evaluate properties of alofanib (gavage; capsules, i.v. injections). 240 rats and 30 rabbits received alofanib (0–40.5 and 0–21.6 mg/kg/day) i.v. daily for 24 weeks. Clinical observations and laboratory parameters were recorded. Necropsy was conducted following treatment/recovery periods, and histologic examinations were performed.


Alofanib significantly inhibited proliferation of FGFR2-expressing cells. Alofanib potently inhibited growth of cells expressing FGFR2 IIIb and IIIc, with GI50 values of 12 and 16 nmol/l, respectively. In preclinical xenograft models, alofanib significantly inhibited aggressive growth of FGFR2 high-expressing SUM52PE breast cancer and SKOV3 ovarian cancer, and had moderate activity in the FGFR2 low-expressing HS578T breast cancer. Treatment with alofanib did not result in the FGFR2-negative NCI-H226 lung cancer and HCT116 colon cancer growth. There was no treatment-related mortality, severe toxicity and significant changes in organs in the 24-week study. Compound was well-tolerated in vivo. Mild hyperphosphatemia was found in female rats. Alofanib suppressed spermatogenesis in male rats. Blood vessel wall inflammation may be caused by alofanib. PK data will be presented at the meeting.


These results provide strong rationale for evaluation of alofanib in patients with FGFR2-expressing cancers.

Clinical trial indentification


Legal entity responsible for the study



Skolkovo Foundation


E. Gavrilova: Employer. All other authors have declared no conflicts of interest.