Basilea Announces Positive Interim Results from Registrational Phase 2 Study with Oncology Drug Candidate Derazantinib in Intrahepatic Cholangiocarcinoma (iCCA)
- 21% objective response rate with six confirmed partial responses from 29 evaluable patients
- 83% disease control rate
- Safety profile and tolerability of continuous dosing schedule confirmed
The interim analysis in the ongoing registrational Phase 2 study was conducted after 42 patients had been enrolled in the study, with a subset of 29 evaluable patients who had at least one post-baseline imaging assessment. The objective response rate (ORR) in the 29 evaluable patients was 21%. The disease control rate (DCR), reflecting the proportion of patients with a partial response or with stable disease, was 83%. The safety data obtained from all 42 patients enrolled to date was consistent with the results from previous clinical studies with derazantinib.
Derazantinib (BAL087, formerly ARQ 087) is an investigational orally administered small molecule inhibitor of the FGFR family of kinases with strong activity against FGFR 1, 2, and 3. Therefore, it is called a pan-FGFR 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 iCCA, bladder, breast, gastric and lung cancers.2 Current scientific literature suggests that FGFR alterations exist in a range of 5% to 30% in these cancers.3 In iCCA, FGFR2 gene fusions have been reported in 13-22% of the cases4, 5 and FGFR gene mutations have been reported in up to 5% of the cases.3 Basilea in-licensed derazantinib from
About intrahepatic cholangiocarcinoma (iCCA)
Intrahepatic cholangiocarcinoma (iCCA) is a cancer originating from the biliary system. The age-adjusted incidence rate of iCCA in
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||ClinicalTrials.gov identifier: NCT03230318|
|2||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|
|3||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|
|4||R. P. Graham, E. G. Barr Fritcher, E. Pestova et al. Fibroblast growth factor receptor 2 translocations in intrahepatic cholangiocarcinoma. Human Pathology 2014 (45), 1630-1638|
|5||A. Jain, M. J. Borad, R. K. Kelley et al. Cholangiocarcinoma with FGFR genetic abberations: a unique clinical phenotype. JCO Precision Oncology 2018 (2), 1-12|
|6||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/s41416-018-0334-0|
|7||S. K. Saha, A. X. Zhu, C. S. Fuchs et al. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. The Oncologist 2016 (21), 594-599|
|8||S. Sahu, W. Sun, Targeted therapy in biliary tract cancers – current limitations and potentials in the future. Journal of Gastrointestinal Oncology 2017 (8), 324-336|
Marc Schegerin, M.D.
Senior Vice President
Head of Strategy, Finance and Communication
Allison Blum, Ph.D.
LifeSci Public Relations