Date: 2014-11-10
Type of information: Results
phase: 2
Announcement: results
Company: Arqule Therapeutics (USA - MA)
Product: tivantinib
Action
mechanism: tyrosine kinase inhibitor. 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.
Disease: prostate cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This trial is 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. The principal investigator was J. Paul Monk, M.D. of The Ohio State University, Arthur G. James Cancer Hospital and Solove Research Institute. (NCT01519414) Patients 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).
Latest
news: * On November 10, 2014, ArQule 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. 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. 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. 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.
