The median progression free survival was 7.2 months and patients received treatment for a median of 8.2 months. This is consistent with results previously reported for derazantinib-treated iCCA patients with FGFR2 gene fusions.4, 5 Derazantinib showed a manageable safety profile with a low incidence of nail toxicity, retinal events, hand-foot syndrome and stomatitis (inflammation of the mouth).
Dr.
Apart from iCCA, Basilea is also exploring derazantinib in two phase 1/2 studies, as monotherapy and in combinations with other cancer treatments, in patients with advanced urothelial cancer (FIDES-02), or advanced gastric cancer (FIDES-03), with FGFR genetic aberrations.
The following e-poster was presented at the | |
Presentation # | Authors/title |
45P | Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: Pooled analysis of clinical trials and early access programs. |
For further information, please visit www.esmo.org/meetings/map-virtual-2020/programme
About derazantinib
Derazantinib is an investigational orally administered small-molecule FGFR inhibitor with strong activity against FGFR1, 2, and 3.6 FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR genetic aberrations, e.g. gene fusions, mutations or amplifications, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial, breast, gastric and lung cancers.7 In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.8
Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).6, 9 CSF1R-mediated signaling is important for the maintenance of tumor-promoting macrophages and therefore has been identified as a potential target for anti-cancer drugs.10 Preclinical data has shown that tumor macrophage depletion through CSF1R blockade renders tumors more responsive to T-cell checkpoint immunotherapy, including approaches targeting PD-L1/PD-1.11, 12
Derazantinib has demonstrated antitumor activity and a manageable safety profile in a previous biomarker-driven phase 1/2 study in iCCA patients,4 and has received
About Basilea
Disclaimer
This communication expressly or implicitly contains certain forward-looking statements, such as "believe", "assume", "expect", "forecast", "project", "may", "could", "might", "will" or similar expressions concerning
For further information, please contact:
Head of | |
Phone | +41 61 606 1102 |
media_relations@basilea.com investor_relations@basilea.com |
This press release can be downloaded from www.basilea.com.
References
- ClinicalTrials.gov identifier: NCT01752920
- FIDES-01: ClinicalTrials.gov identifier: NCT03230318
- Early access program: ClinicalTrials.gov identifier: NCT04087876
- V. Mazzaferro, B. F. El-Rayes, M. Droz dit Busset et al. Derazantinib (ARQ 087) in advanced or inoperable FGFR2 gene fusion-positive intrahepatic cholangiocarcinoma.
British Journal of Cancer 2019 (120), 165-171. ClinicalTrials.gov identifier: NCT01752920 M. Droz Dit Busset ,S. Braun ,B. El-Rayes et al. Annales of Oncology 2019 (30) suppl_5, v253–v324.- T. G. Hall, Y. Yu, S. Eathiraj et al. Preclinical activity of ARQ 087, a novel inhibitor targeting FGFR dysregulation. PLoS ONE 2016, 11 (9), e0162594
- R. Porta, R. Borea, A. Coelho et al. FGFR a promising druggable target in cancer: Molecular biology and new drugs. Critical Reviews in Oncology/Hematology 2017 (113), 256-267
- T. Helsten, S. Elkin, E. Arthur et al. The FGFR landscape in cancer: Analysis of 4,853 tumors by next-generation sequencing.
Clinical Cancer Research 2016 (22), 259-267 - P. McSheehy, F. Bachmann, N. Forster-Gross et al. Derazantinib (DZB): A dual FGFR/CSF1R-inhibitor active in PDX-models of urothelial cancer. Molecular Cancer Therapeutics 2019 (18), 12 supplement, pp. LB-C12
- M. A. Cannarile, M. Weisser, W. Jacob et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
Journal for ImmunoTherapy of Cancer 2017, 5:53 - Y. Zhu, B. L. Knolhoff, M. A. Meyer et al. CSF1/CSF1R Blockade reprograms tumor-infiltrating macrophages and improves response to T cell checkpoint immunotherapy in pancreatic cancer models.
Cancer Research 2014 (74), 5057-5069 - E. Peranzoni, J. Lemoine, L. Vimeux et al. Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment. Proceedings of the
National Academy of Science of the United States of America 2018 (115), E4041-E4050 - FIDES-02: ClinicalTrials.gov identifier: NCT04045613
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- Press release (PDF)
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