ArQule Announces Dosing in a Registrational Trial of FGFR Inhibitor, Derazantinib, for Treatment of Intrahepatic Cholangiocar...
November 21 2017 - 7:00AM
Business Wire
The trial is being conducted with a biomarker
assay to identify FGFR2 fusions
ArQule, Inc. (Nasdaq: ARQL) today announced dosing of the
initial patients in a registrational trial with its FGFR inhibitor,
derazantinib (ARQ 087) in FGFR2 fusion driven second-line
intrahepatic Cholangiocarcinoma (iCCA). The trial is planned to
enroll up to 100 iCCA patients and provides an opportunity for a
conditional approval as part of a fast-to-market strategy.
Derazantinib is a multi-kinase inhibitor designed to preferentially
inhibit the fibroblast growth factor receptor (FGFR) family.
The open-label single-arm trial will be recruiting initially in
the U.S. and subsequently in Europe with objective response rate
(ORR) as the primary endpoint. Derazantinib will be dosed orally
once a day at 300 mg. FGFR2 fusion status will be determined by a
break apart FISH assay. An interim analysis will be performed after
the first 40 patients have been enrolled and evaluated for
response.
“iCCA is a rare and difficult disease to treat,” said Dr. Brian
Schwartz, M.D., Head of Research and Development and Chief Medical
Officer at ArQule. “The durable response rate of 21% we observed in
the phase 1/2 iCCA FGFR2 fusion driven trial has lead us to design
the first registrational trial with a biomarker for this patient
population. We are happy to report that recruitment is off to a
great start with four patients already dosed.”
Patients with advanced iCCA who relapse after first-line
multi-agent chemotherapy have limited treatment options with poor
prognosis. In recent years, FGFR2 fusions have been recognized as a
potential iCCA-specific therapeutic target. The company has been
granted orphan drug designation by the U.S. Food and Drug
Administration and European Medicines Agency for derazantinib in
this indication.
About Intrahepatic Cholangiocarcinoma
Cholangiocarcinoma (CCA) is the most common biliary malignancy
and the second most common hepatic malignancy after hepatocellular
carcinoma (HCC)1. Depending on the anatomic location, CCA is
classified as intrahepatic (iCCA), perihilar (pCCA), and
extrahepatic (eCCA). iCCA originates from the intrahepatic biliary
ductal system and forms an intrahepatic mass. The average age
adjusted incidence rate for iCCA is approximately one in 100,000
per year in the United States and Europe2,3.
About FGFR and Derazantinib (ARQ 087)
Derazantinib is a multi-kinase inhibitor designed to
preferentially inhibit the fibroblast growth factor receptor
(“FGFR”) family with demonstrated efficacy in FGFR2 genetic
alterations. The FGFR pathway is disrupted in several ways in human
cancer, thus providing numerous therapeutic targets for an
inhibitor of this pathway. Derazantinib has demonstrated in vivo
inhibition of tumor growth and downstream signaling in tumors whose
growth is driven by FGFR.
Signals of single agent activity with this drug were observed in
phase 1a testing. Phase 1b expansion cohorts with derazantinib
include patients with cholangiocarcinoma and adrenocortical tumors,
as well as those with FGFR translocations, amplifications and
mutations. Clinical development of derazantinib advanced into phase
2 for intrahepatic cholangiocarcinoma (iCCA) in patients with FGFR2
fusions following the observation of two confirmed responses in
this patient population in the phase 1 portion of the program and a
registrational trial is being conducted in this same patient
population.
About ArQule
ArQule is a biopharmaceutical company engaged in the research
and development of targeted therapeutics to treat cancers and rare
diseases. ArQule’s mission is to discover, develop and
commercialize novel small molecule drugs in areas of high unmet
need that will dramatically extend and improve the lives of our
patients. Our clinical-stage pipeline consists of five drug
candidates, all of which are in targeted, biomarker-defined patient
populations, making ArQule a leader among companies our size in
precision medicine. ArQule’s proprietary pipeline includes:
Derazantinib, a multi-kinase inhibitor designed to preferentially
inhibit the fibroblast growth factor receptor (FGFR) family, in a
registrational trial for iCCA and in phase 1b for multiple oncology
indications; Miransertib (ARQ 092), a selective inhibitor of the
AKT serine/threonine kinase, in a phase 1/2 company sponsored study
for Overgrowth Diseases, in a phase 1 study for ultra-rare Proteus
syndrome conducted by the National Institutes of Health (NIH), as
well as in multiple oncology indications; ARQ 751, a next
generation AKT inhibitor, in phase 1 for patients with AKT1 and
PI3K mutations; and ARQ 761, a β-lapachone analog being evaluated
as a promoter of NQO1-mediated programmed cancer cell necrosis, in
phase 1/2 in multiple oncology indications in partnership with the
University of Texas Southwestern Medical Center. In addition, we
have advanced ARQ 531, an investigational, orally bioavailable,
potent and reversible inhibitor of both wild type and C481S-mutant
BTK, in phase 1 for patients with B-cell malignancies refractory to
other therapeutic options. ArQule’s current discovery efforts are
focused on the identification and development of novel kinase
inhibitors, leveraging the Company’s proprietary library of
compounds. You can follow us on Twitter and LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements regarding
the Company’s clinical trials with derazantinib. 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 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 view of the data or require additional data or
information or additional studies. In addition, we 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 intend to outsource the development of such
companion diagnostics to one or more third party collaborators.
There can be no assurance that we will successfully enter into an
agreement or agreements with any such collaborators; in addition,
any such collaborator may encounter difficulties in developing and
obtaining approval for such companion diagnostic, 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
diagnostic could delay or prevent approval of derazantinib. 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
Securities and Exchange Commission. The Company does not undertake
any obligation to publicly update any forward-looking
statements.
1 Welzel TM, et al. Impact of classification of hilar
cholangiocarcinomas (Klatskin tumors) on the incidence of intra-
and extrahepatic cholangiocarcinoma in the United States. J
Natl Cancer Inst. 2006; 98(12),873–875.2 National
Cancer Institute: Surveillance, Epidemiology, and End Results3
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ArQule, Inc.Dawn Schottlandt, 781-994-0300Vice President,
Investor Relations/Corp. Communicationswww.ArQule.com
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