Basilea Announces Collaboration to Study Derazantinib and Atezolizumab (Tecentriq®) in Urothelial Cancer
The planned study will assess the safety, tolerability and efficacy of
the derazantinib-atezolizumab combination in patients with advanced
urothelial cancer and confirmed FGFR genomic aberrations. Basilea will
be the sponsor of the study, and
Derazantinib was licensed to
Derazantinib (BAL087, formerly ARQ 087) is an investigational orally administered small molecule inhibitor of the FGFR family of kinases with strong activity against FGFR1, 2, and 3. Therefore, it is called a panFGFR kinase inhibitor. FGFR kinases are key drivers of cell proliferation, differentiation and migration. FGFR alterations, e.g. gene fusions, overexpression or mutations, have been identified as potentially important therapeutic targets for various cancers, including intrahepatic cholangiocarcinoma (iCCA), urothelial (bladder), breast, gastric and lung cancers.1 Current scientific literature suggests that FGFR alterations exist in a range of 5% to 30% in these cancers.2 In addition, derazantinib inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R). 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.3 Moreover, pre-clinical 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-1.3, 4, 5 Basilea in-licensed derazantinib from
About urothelial cancer
Urothelial cancer is the sixth most common cancer in the U.S. These cancers start in the urothelial cells that line the inside of the bladder. 80,000 new cases of bladder cancer have been estimated in the U.S. for 2017. Up to 20 percent of patients will have muscle-invasive disease and present with or will later develop metastases.7 For patients with metastatic disease, outcomes can be poor due to the often rapid progression of the tumor and the lack of efficacious treatments, especially in relapsed or refractory disease.
Forward Looking Statements
This press release contains forward-looking statements regarding clinical trials with derazantinib as well as the potential for future milestone and royalty payments under the Company’s exclusive license agreement with Basilea. These statements are based on the Company’s current beliefs and expectations and are subject to risks and uncertainties that could cause actual results to differ materially. Positive information about pre-clinical and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, derazantinib may not demonstrate promising therapeutic effect. In addition, derazantinib may not demonstrate an acceptable safety profile in current or later stage or larger scale clinical trials as a result of known or as yet unanticipated side effects. The results achieved in later stage trials may not be sufficient to meet applicable regulatory standards or to justify further development. Problems or delays may arise during clinical trials or in the course of developing, testing or manufacturing derazantinib that could lead the Company or Basilea to discontinue its development. Even if later stage clinical trials are successful, unexpected concerns may arise from subsequent analysis of data or from additional data. Obstacles may arise or issues may be identified in connection with review of clinical data with regulatory authorities. Regulatory authorities may disagree with the Company’s or Basilea’s view of the data or require additional data or information or additional studies. In addition, we or Basilea plan to develop and use a companion diagnostic to identify patients with FGFR2 fusions and possibly other fusions for our future derazantinib clinical trials. We or Basilea intend to outsource the development of such companion diagnostics to one or more third party collaborators. Such collaborators may encounter difficulties in developing and obtaining approval for such companion diagnostics, including issues relating to selectivity/specificity, analytical validation, reproducibility, concordance or clinical validation. Any delay or failure to develop or obtain regulatory approval of such companion diagnostics could delay or prevent approval of derazantinib.Moreover, Basilea has only a limited track record of drug development in oncology. If derazantinib is not successfully developed and as a result of any of the foregoing or other issues, risks or uncertainties, ArQule may not receive any future milestones or royalties under the license agreement with Basilea.Drug development involves a high degree of risk. Only a small number of research and development programs result in the commercialization of a product. Furthermore, ArQule may not have the financial or human resources to successfully pursue drug discovery in the future. For more detailed information on the risks and uncertainties associated with the Company’s drug development and other activities, see the Company’s periodic reports filed with the
|1||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|
|2||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|
|3||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|
|4||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|
|5||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), E-4041-E4050|
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. Published online on November 13, 2018. https://doi.org/10.1038/s41416-018-0334-05
|7||B. Dietrich, S. Srinivas. Urothelial carcinoma: the evolving landscape of immunotherapy for patients with advanced disease. Research and reports in urology 2018 (10), 7-16|
Marc Schegerin, M.D.
Senior Vice President
Head of Strategy, Finance and Communication
Allison Blum, Ph.D.
LifeSci Public Relations (646) 627-8383