ArQule Announces Interim Phase 2 Study Results for Tivantinib in Combination with Cetuximab in Patients with MET-High, KRAS Wild Type Colorectal Cancer Presented at ESMO World Congress on Gastrointestinal Cancer 2015
- Stage 1 endpoint of Objective Response Rate (ORR) met, study proceeding to Stage 2.
- Preliminary results support hypothesis that MET inhibition can reverse resistance to EGFR inhibitors.
"Considering that in CRC objective response rate (ORR) often correlates
with overall survival (OS) benefit, the preliminary results obtained
combining tivantinib with cetuximab are encouraging," said
The primary endpoint of the trial is ORR in the biomarker defined population. Secondary study endpoints are progression-free survival (PFS), overall survival (OS) and safety. The ESMO World GI presentation included data from 21 patients enrolled in Stage 1 of this trial. One patient, still on therapy, experienced a complete response (CR) and 2 patients experienced durable confirmed partial responses (PRs). Stable disease was observed in 8 patients, including 2 short duration PRs, for an overall Disease Control Rate (CR + PR + SD) of 52.4%. Having met the Stage 1 endpoint (≥2 confirmed responses), the trial continued to Stage 2 and has recently completed enrollment.
Adverse events were in line with those historically reported, including skin toxicity attributed to cetuximab, and neutropenia attributed to tivantinib. Neutropenia was addressed timely with growth factors and dose adjustments.
The trial is a 2-stage, investigator-initiated study testing tivantinib
plus cetuximab after recent progression on anti-EGFR antibodies. The
trial is coordinated by the
About Colorectal Cancer (CRC)
Colorectal cancer is the second leading cause of cancer-related deaths
in the U.S. and is the third most common cancer in men and women.
According to the
About MET and tivantinib (ARQ 197)
Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in Phase 2 and Phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.
Pre-clinical data have demonstrated that tivantinib inhibits 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 generally well tolerated and has shown clinical activity in the tumors studied. Tivantinib has not yet been approved for any indication in any country.
This press release contains forward-looking statements regarding the
Company's clinical trials with tivantinib (ARQ 197). 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 effect or 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 prior to the initiation of planned clinical trials,
during clinical trials or in the course of developing, testing or
manufacturing that could lead the Company or its partners and
collaborators to fail to initiate or 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
Chief Financial Officer and Treasurer
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