ArQule Announces Tivantinib Meets Primary Endpoint, Significantly Extending Time to Progression in Phase 2 Trial in Second-Line Hepatocellular Carcinoma
Adverse events were reported at similar rates in the treatment and placebo arms, except for a higher incidence of fatigue and hematologic events, including neutropenia and anemia, in tivantinib-treated patients. The incidence of hematologic events declined following dose reduction of tivantinib from 360 milligrams twice daily (BID) to 240 milligrams BID.
"These findings represent the first randomized data reported with a
c-Met inhibitor administered as a single agent in HCC," said Dr.
The 107 patients in this trial had unresectable HCC and had experienced disease progression after first-line therapy or were unable to tolerate such therapy. At the start of the study, patients were randomized to receive tivantinib at 360 milligrams BID or placebo. As previously disclosed, due to the rate of neutropenia, the tivantinib dose was reduced to 240 milligrams BID for all patients. TTP was defined as the time from patient randomization until objective tumor progression using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria evaluated by central radiological review.
About Hepatocellular Carcinoma (HCC)
Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. The incidence is increasing, and HCC has risen to become the fifth most common malignancy worldwide and the third leading cause of cancer-related death, exceeded only by cancers of the lung and stomach.1 The estimated incidence is about 500,000-1,000,000 new cases per year, causing 600,000 deaths globally per year. Chronic hepatitis B and C are recognized as the major factors worldwide increasing the risk of HCC, with risk being even greater in the presence of co-infection with these viruses2. Cirrhosis is also a risk factor for development of HCC.
About c-Met and Tivantinib (ARQ 197)
Tivantinib is an orally available, selective inhibitor of c-Met, a receptor tyrosine kinase, which is currently in Phase 2 and Phase 3 clinical trials. In certain healthy adult cells, c-Met is present in low to normal levels to support natural cellular function and renewal, but in some cancer cells, c-Met is inappropriately and continuously activated. When thus abnormally activated, c-Met plays multiple roles in human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis.
Pre-clinical data have demonstrated that tivantinib inhibits c-Met activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been well tolerated and has shown clinical activity in the tumors studied.
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This press release contains forward-looking statements regarding the
Company's clinical trials with tivantinib and its agreement with Daiichi
Sankyo Co., Ltd. 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, tivantinib may not demonstrate promising
therapeutic effects in such trials; in addition, it may not demonstrate
an appropriate safety profiles in later stage or larger scale clinical
trials, including among patients with underlying cirrhosis and
compromised liver function, 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 tivantinib that could
lead the Company or its partners to discontinue development. Even
if later stage clinical trials are successful, unexpected concerns may
arise from 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, and 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 or Daiichi Sankyo, its partner, to
enroll patients, enter into agreements with clinical trial sites and
investigators, and overcome other technical hurdles and issues related
to the conduct of the trials for which each of them is responsible that
may not be resolved. 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,
1 Hepatocellular carcinoma: Epidemiology, risk factors and
2 Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-37, 1999.
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