Basilea reports positive interim results from phase 2 study FIDES-01 for derazantinib in FGFR2 gene mutation- or amplification-positive patients with bile duct cancer (iCCA)

• Disease control rate of 79% with one complete response
  
  
• Consistent safety and tolerability profile
  
  
• Study continues with topline results expected in H1 2022
  
  

Basel, Switzerland, March 24, 2021

Basilea Pharmaceutica Ltd. (SIX: BSLN) announced today positive results of a pre-planned interim analysis in cohort 2 of the phase 2 study FIDES-01 (Fibroblast growth factor Inhibition with DErazantinib in Solid tumors), which is assessing the anti-tumor efficacy of the orally administered fibroblast growth factor receptor (FGFR) inhibitor, derazantinib, in patients with inoperable or advanced intrahepatic cholangiocarcinoma (iCCA), a form of bile duct cancer.¹ After cohort 1 of the study provided the clinical proof of concept for derazantinib monotherapy in the treatment of iCCA patients with FGFR2 gene fusions, cohort 2 is enrolling iCCA patients with FGFR2 gene mutations or amplifications.² The efficacy data obtained in the interim analysis met the pre-specified threshold so that the study will proceed to the next stage as planned.

The interim analysis of cohort 2 is based on 14 evaluable patients who had at least one post-baseline tumor assessment. The pre-specified criterion that at least 8 patients met the primary endpoint of obtaining progression-free survival (PFS) of at least 3 months was successfully achieved. The positive interim analysis allows the study to advance to its next stage and enrol a total of 43 patients. As a number of patients are still ongoing with treatment the median PFS was not yet mature at the time of the interim analysis and will be defined at a later time point.

The disease control rate (DCR), reflecting the proportion of patients with a complete or partial response or with stable disease, was 79%, including one patient with a confirmed complete response, one patient with an unconfirmed partial response and nine patients with a best response of stable disease at the time when the interim analysis was conducted.

The observed safety and tolerability is consistent with the profile reported for cohort 1.

Dr. Marc Engelhardt, Chief Medical Officer, said: “We are very pleased with the positive interim results for this cohort of iCCA patients with FGFR2 gene mutations or amplifications. The clinical benefit with derazantinib is similar to that reported for iCCA patients with FGFR2 gene fusions earlier this year. This supports the relevance of derazantinib in a group of patients with iCCA where there has been very limited clinical evidence of successful treatment with other FGFR inhibitors and confirms the broad potential of derazantinib as a monotherapy for the treatment of iCCA patients with diverse FGFR2 genetic aberrations. This outcome is very encouraging and further strengthens the evidence for the differentiation of derazantinib versus other FGFR inhibitors both from the efficacy and safety perspective. We are now progressing the study to the next stage and expect topline results for cohort 2 in the first half of 2022.”

About derazantinib

Derazantinib is an investigational orally administered small-molecule FGFR inhibitor with strong activity against FGFR1, 2, and 3.³ 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.⁴ In these cancers, FGFR genetic aberrations are found in a range of 5% to 30%.⁵
Derazantinib also inhibits the colony-stimulating-factor-1-receptor kinase (CSF1R).^{3, 6} 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.⁷ 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.^8,9
Derazantinib has demonstrated antitumor activity and a manageable safety profile in a previous biomarker-driven phase 1/2 study in iCCA patients,¹⁰ and has received U.S. and EU orphan drug designation for iCCA. Basilea is currently conducting three clinical studies with derazantinib. The first study, FIDES-01, is a phase 2 study in patients with inoperable or advanced iCCA. It comprises one cohort of patients with FGFR2 gene fusions and another cohort of patients with mutations or amplifications.¹ The second study, FIDES-02, is a phase 1/2 study evaluating derazantinib alone and in combination with Roche's PD-L1 checkpoint inhibitor, atezolizumab, in patients with advanced urothelial cancer, including metastatic, or recurrent surgically unresectable disease, expressing FGFR genetic aberrations.¹¹ The third study, FIDES-03, is a phase 1/2 study evaluating derazantinib alone and in combination with Lilly’s anti-VEGFR2 antibody ramucirumab and paclitaxel, or with Roche’s PD-L1 checkpoint inhibitor atezolizumab, in patients with advanced gastric cancer with FGFR genetic aberrations.¹² Basilea has in-licensed derazantinib from ArQule Inc., a wholly-owned subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a cancer originating from the biliary system. The age-adjusted incidence rate of iCCA in the United States has been increasing over the past decade and is currently estimated to be approximately 1.2 per 100,000.¹³ Patients are often diagnosed with advanced or metastatic disease that cannot be surgically removed. Current first-line standard of care is the chemotherapy combination of gemcitabine and platinum-derived agents. The prognosis for patients with advanced disease is poor, with a median survival of less than one year.¹⁴

About Basilea

Basilea is a commercial-stage biopharmaceutical company founded in 2000 and headquartered in Switzerland. We are committed to discovering, developing and commercializing innovative drugs to meet the medical needs of patients with cancer and infectious diseases. We have successfully launched two hospital brands, Cresemba for the treatment of invasive fungal infections and Zevtera for the treatment of severe bacterial infections. We are conducting clinical studies with two targeted drug candidates for the treatment of a range of cancers and have a number of preclinical assets in both cancer and infectious diseases in our portfolio. Basilea is listed on the SIX Swiss Exchange (SIX: BSLN). Please visit basilea.com.

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 Basilea Pharmaceutica Ltd. and its business, including with respect to the progress, timing and completion of research, development and clinical studies for product candidates. Such statements involve certain known and unknown risks, uncertainties and other factors, which could cause the actual results, financial condition, performance or achievements of Basilea Pharmaceutica Ltd. to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Basilea Pharmaceutica Ltd. is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise. Derazantinib and its uses are investigational and have not been approved by a regulatory authority for any use. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in nonclinical/preclinical studies to humans is currently being evaluated.

For further information, please contact:

Peer Nils Schröder, PhD Head of Corporate Communications & Investor Relations
Phone	+41 61 606 1102
E-mail	media_relations@basilea.com investor_relations@basilea.com

This press release can be downloaded from www.basilea.com.

References

1. FIDES-01: ClinicalTrials.gov identifier: NCT03230318
2. Topline results of cohort 1 of the FIDES-01 study were published on February 10, 2021 (see press release)
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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
11. FIDES-02: ClinicalTrials.gov identifier: NCT04045613
12. FIDES-03: ClinicalTrials.gov identifier: NCT04604132
13. 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
14. A. Lamarca, D. H. Palmer, H. S. Wasa et al. ABC-06 | A randomised phase III, multi-centre, open-label study of Active Symptom Control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced/metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy. Journal of Clinical Oncology 2019 (37), supplement, abstract 4003 

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