ArQule, Inc. (NASDAQ: ARQL) today announced positive top-line results
from a randomized, double-blind, placebo-controlled Phase 2 clinical
trial of tivantinib as a single agent in metastatic prostate cancer.
This trial (clinicaltrials.gov identifier NCT01519414) was conducted
under a Cooperative Research and Development Agreement (CRADA) with the
National Cancer Institute’s Cancer Therapy Evaluation Program (CTEP) (“A
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of ARQ 197
(tivantinib) in Men with Asymptomatic or Minimally Symptomatic
Metastatic Castrate Resistant Prostate Cancer,” NCI Protocol # 8986).
The principal investigator was J. Paul Monk, M.D. of The Ohio State
University, Arthur G. James Cancer Hospital and Solove Research
Institute.
In this trial, 78 patients were randomized 2 to 1 to receive either
tivantinib as a single agent or placebo. During a pre-planned analysis,
it was found that the trial met its primary endpoint of improving median
progression-free survival (PFS) with tivantinib alone as compared to
placebo. The results were highly statistically significant. Safety data
were consistent with those observed in other trials of tivantinib.
The results of the trial are the subject of ongoing analyses and will be
submitted by the investigators for presentation at a future medical
conference. As final data emerge from this trial, ArQule and its
partner, Daiichi Sankyo Company, Limited, will discuss with the National
Institutes of Health (NIH) the potential for additional trials in this
indication.
“We are pleased that these significant findings from the NIH trial in
prostate cancer add to the body of clinical evidence of the anti-cancer
activity of tivantinib across multiple tumor types,” said Paolo Pucci,
chief executive officer of ArQule.
“Our CRADA reflects our shared commitment with the NCI to continue to
explore the clinical potential of tivantinib in tumor types beyond the
compound’s lead indication, hepatocellular carcinoma (HCC), currently in
Phase 3 clinical trials,” said Mr. Pucci.
Uncontrolled, signal generation data from additional NIH-sponsored
trials with tivantinib in breast cancer and multiple myeloma did not
meet their primary endpoint of response rate. As a result, the Company
does not plan to prioritize development in these indications at this
time.
About the NCI Protocol # 8986 Trial
This study is a randomized Phase 2 trial in which men with asymptomatic
or minimally symptomatic metastatic castrate resistant,
chemotherapy-naïve prostate cancer were randomized 2 to 1 to receive
tivantinib 360 milligrams BID or placebo. The primary objective of the
trial is PFS. Secondary objectives include PSA response rate at 12
weeks, radiographic response rate at 12 weeks, proportion of patients
who are progression-free at 12 weeks, and safety and tolerability.
The study is designed to detect an improvement in the median PFS from 3
months to 6 months with tivantinib treatment. The proposed sample of 78
patients (26 in the placebo arm, 52 in the tivantinib arm) provides 90
percent power to detect an improvement from 3 months median PFS with
placebo to a median PFS of at least 6 months with tivantinib. This
design is based on the assumption of having 58 cumulative events
(progressions or deaths).
About Tivantinib and the MET pathway
Tivantinib is an orally administered, selective inhibitor of MET, a
receptor tyrosine kinase. Tivantinib is currently in Phase 3 development
and has not yet been approved in any market. In healthy adult cells, MET
is present in normal levels to support natural cellular function, but in
cancer cells MET is inappropriately and continuously activated for
unknown reasons. When abnormally activated, MET plays multiple roles in
aspects of human cancer, including cancer cell growth, survival,
angiogenesis, invasion and metastasis.
About ArQule and Daiichi Sankyo Co., Ltd.
In December 2008, ArQule and Daiichi Sankyo signed a license,
co-development and co-commercialization agreement for tivantinib (ARQ
197) in the U.S., Europe, South America and the rest of the world,
excluding Japan, China (including Hong Kong), South Korea and Taiwan.
About ArQule
ArQule is a biotechnology company engaged in the research and
development of next-generation, small-molecule cancer therapeutics. The
Company’s targeted, broad-spectrum products and research programs are
focused on key biological processes that are central to human cancers.
ArQule’s lead product, in Phase 2 and Phase 3 clinical development, is
tivantinib (ARQ 197), an oral, selective inhibitor of the c-MET receptor
tyrosine kinase. The Company’s pipeline includes: ARQ 092, designed to
inhibit the AKT serine/threonine kinase, and ARQ 087, a multi-kinase
inhibitor designed to preferentially inhibit the fibroblast growth
factor receptor (FGFR) family. ArQule’s current discovery efforts are
focused on the identification of novel kinase inhibitors, leveraging the
Company’s proprietary library of compounds.
This press release contains forward-looking statements regarding the
Company’s clinical trials with tivantinib (ARQ 197), including clinical
trials in prostate cancer, and as well as its ability to fund operations
with current cash and marketable securities. 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, including in prostate cancer, does not
ensure that later stage or larger scale clinical trials will be
successful. For example, tivantinib may not demonstrate promising
therapeutic effect; in addition, it may not demonstrate appropriate
safety profiles 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 these compounds that could lead the
Company or its partners, including the National Institutes of Health, to
discontinue 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, the planned timing of initiation and
completion of clinical trials for tivantinib is subject to the ability
of the Company as well as Daiichi Sankyo, Inc. and Kyowa Hakko Kirin, a
licensee of tivantinib, to enroll patients, enter into agreements with
clinical trial sites and investigators, and overcome technical hurdles
and other issues related to the conduct of the trials for which each of
them is responsible. There is a risk that these issues may not be
successfully resolved. In addition, we and our partners are
utilizing a companion diagnostic to identify MET-high patients in the
METIV-HCC and JET-HCC trials, and we may encounter difficulties in
developing and obtaining approval for companion diagnostics, including
issues relating to selectivity/specificity, analytical validation,
reproducibility, or clinical validation. Any delay or failure by our
collaborators to develop or obtain regulatory approval of the companion
diagnostics could delay or prevent approval of our product candidates.
Drug development involves a high degree of risk. Only a small number
of research and development programs result in the commercialization of
a product. Positive pre-clinical data may not be supported in
later stages of development. Furthermore, ArQule may not have the
financial or human resources to successfully pursue drug discovery in
the future. Moreover, with respect to partnered programs, even if
certain compounds show initial promise, Daiichi Sankyo or Kyowa Hakko
Kirin may decide not to license or continue to develop them, as the case
may be. In addition, Daiichi Sankyo and Kyowa Hakko Kirin have
certain rights to unilaterally terminate their agreements with ArQule.
If either company were to do so, the Company might not be able to
complete development and commercialization of the applicable licensed
products on its own. 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.
Copyright Business Wire 2014