Press Release: Basilea reports activity of derazantinib in preclinical models of gastric cancer at ASCO Gastrointestinal Cancers Symposium

Basilea Pharmaceutica

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Basel, Switzerland, January 23, 2020 -- Basilea Pharmaceutica Ltd. (SIX:

BSLN) reported today that its oncology drug candidate derazantinib

showed convincing activity in preclinical models of gastric cancer with

FGFR genetic aberrations. The data will be presented at the

Gastrointestinal Cancers Symposium of the American Society of Clinical

Oncology (ASCO), which takes place January 23-25, 2020, in San Francisco,

USA.

Dr. Laurenz Kellenberger, Basilea's Chief Scientific Officer, said: "The

preclinical data presented at the ASCO symposium show that derazantinib

has the potential to provide clinical benefit in gastric cancer with

FGFR genetic aberrations. Based on this convincing data we recently

announced our intention to start a phase 1/2 study with derazantinib in

patients with advanced gastric cancer in the third quarter of 2020."

The preclinical data were generated in patient-derived mouse models of

biliary, gastric and colorectal cancer with FGFR gene fusions, mutations

and amplifications. Derazantinib was well tolerated and led to strong

responses in several animal models, particularly in gastric cancer

models with FGFR2 gene fusions, where responses included complete tumor

regression.

Gastric cancer is the fifth most common cancer worldwide and the third

most lethal cancer type.(1) Median survival rarely exceeds twelve months

and the five-year-survival is less than 10%.(2) Basilea estimates that

there are approximately 190,000 new cases of gastric cancer per year in

total across the EU top 5 countries, Japan and the U.S. FGFR genetic

aberrations have been observed in about 10% of gastric cancers.(3)

A second abstract at the symposium provides an update on the ongoing

registrational phase 2 study FIDES-01 (Fibroblast growth factor

Inhibition with DErazantinib in Solid tumors) with derazantinib in

intrahepatic cholangiocarcinoma (iCCA) patients. The multicenter,

multicohort open-label study is planned to enroll 43 patients with

mutations or amplifications of the FGFR2 gene confirmed by

next-generation sequencing. In addition, the study includes a cohort of

approximately 100 patients with FGFR2 gene fusion positive iCCA.

To date, FGFR inhibitors have demonstrated clinical activity in FGFR2

gene fusion-driven iCCA. Therefore, assessing the activity of

derazantinib in FGFR2 gene mutations or amplifications is important to

further define the full therapeutic potential of derazantinib in iCCA.

Topline data for the cohort with FGFR2 gene fusion-positive patients and

interim data for the cohort with FGFR2 gene mutations or amplifications

are expected to become available in the second half of 2020.

Intrahepatic cholangiocarcinoma 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.(4) Patients are often diagnosed with

advanced or metastatic disease that cannot be surgically removed. FGFR2

gene fusions have been reported in 13-22% of iCCA cases.(5, 6) 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

with chemotherapy.(7) There is no proven effective treatment for

patients who progress on first-line chemotherapy, thus there is a high

unmet medical need.(8)

Derazantinib abstracts at the 2020 ASCO GI Cancers Symposium

Thursday, 23 January 2020 -- 12:00-1:30 p.m. PST

Poster Session A

-- The FGFR-inhibitor, derazantinib (DZB), is active in

PDX-models of GI-cancer with specific aberrations in

FGFR -- Paul McSheehy, Felix Bachmann, Nicole

Forster-Gross, Mahmoud El Shemerly, Mila Roceri,

Laurenz Kellenberger, Heidi Lane; abstract 421,

poster G10

Friday, 24 January 2020 -- 12:00-1:30 p.m.PST

Trial in Progress Poster Session B

-- FIDES-01, a phase 2 study of derazantinib in patients

with unresectable intrahepatic cholangiocarcinoma

(iCCA) and FGFR2 fusions and mutations or

amplifications (M/A) -- Walid L. Shaib, Christoph

Gahlemann, Andrea Boncompagni, Silke Friedmann,

Stephan Braun, Marc Engelhardt, Ghassan K. Abou-Alfa,

Mitexh J. Borad; abstract TPS597, poster P10

(ClinicalTrial.gov identifier: NCT03230318)

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For further information, please visit

https://meetings.asco.org/gi/abstracts-posters.

About derazantinib

Derazantinib (formerly ARQ 087) is an investigational orally

administered small-molecule panFGFR kinase inhibitor with strong

activity against FGFR1, 2, and 3.(9) 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.(10) In these cancers, FGFR genetic

aberrations are found in a range of 5% to 30%.(11)

Derazantinib also inhibits the colony-stimulating-factor-1-receptor

kinase (CSF1R).(9, 12) 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.(13) 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.(14, 15) Derazantinib has

demonstrated antitumor activity and a manageable safety profile in

previous clinical studies, including a biomarker-driven phase 1/2 study

in iCCA patients,(16) and has received U.S. and EU orphan drug

designation for iCCA. Basilea is currently conducting two clinical

studies with derazantinib. The first study, FIDES-01, is a

registrational 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.(17) The

second study, FIDES-02, is a phase 1/2 study evaluating derazantinib

alone and in combination with Roche's PD-L1-blocking immune-checkpoint

inhibitor atezolizumab (Tecentriq(R) ) in patients with advanced

urothelial cancer, including metastatic, or recurrent surgically

unresectable disease, expressing FGFR genetic aberrations.(18) Basilea

in-licensed derazantinib from ArQule Inc, a wholly-owned subsidiary of

Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About Basilea

Basilea Pharmaceutica Ltd. is a commercial stage biopharmaceutical

company, focused on the development of products that address the medical

challenges in the therapeutic areas of oncology and infectious diseases.

With two commercialized drugs, the company is committed to discovering,

developing and commercializing innovative pharmaceutical products to

meet the medical needs of patients with serious and life-threatening

conditions. Basilea Pharmaceutica Ltd. is headquartered in Basel,

Switzerland and listed on the SIX Swiss Exchange (SIX: BSLN). Additional

information can be found at Basilea's website www.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

achieveSHYments 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.

For further information, please contact:

Peer Nils Schröder, PhD

Head of Corporate Communications & Investor Relations

+41 61 606 1102

media_relations@basilea.com

investor_relations@basilea.com

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

References

1 F. M Johnston, M. Beckman. Updates on management of gastric cancer.

Current Oncology Reports 2019 (21), 67

2 M. Orditura, G. Galizia, V. Sforza et al. Treatment of gastric

cancer, World Journal of Gastroenterology 2014 (20), 1635-1649

3 A. Bass, V. Thorsson, I. Shmulevich et al. Comprehensive molecular

characterization of gastric adenocarcinoma. Nature 2014 (513), 202-209

4 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

5 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

6 A. Jain, M. J. Borad, R. K. Kelley et al. Cholangiocarcinoma with

FGFR genetic aberrations: a unique clinical phenotype. JCO Precision

Oncology 2018 (2), 1-12

7 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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