Clinical Trials

Date: 2017-02-17

Type of information: Results

phase: 3

Announcement: results

Company: ArQule (USA - MA) Daiichi Sankyo (Japon)

Product: tivantinib (ARQ 197)

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. In December 2008 , ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S. , Europe , South America and the rest of the world, excluding Japan , China (including Hong Kong ), South Korea and Taiwan . In November 2015 , ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.

Disease: hepatocellular carcinoma

Therapeutic area: Cancer - Oncology

Country: Argentina, Australia, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Netherlands, New Zealand, Portugal, Spain, Sweden, Switzerland, USA

Trial details: METIV-HCC is a biomarker-selected, double-blind, placebo-controlled, randomized phase 3 study evaluating tivantinib (2:1) versus best supportive care in patients with MET-overexpressing, inoperable hepatocellular carcinoma intolerant to or previously-treated with systemic therapy. A total of 340 patients with MET overexpressing hepatocellular carcinoma analyzed by a validated immunohistochemical assay were randomized in the intent to-treat population for efficacy analysis. The primary endpoint of the study is overall survival. Secondary endpoints include progression-free survival and safety. (NCT01755767)

Latest news:

•  On February 17, 2017, ArQule and Daiichi Sankyo announced that the METIV-HCC phase 3 study of tivantinib in hepatocellular carcinoma did not meet its primary endpoint of improving overall survival. Full results from the trial will be presented at an upcoming scientific forum.
•  On November 7, 2016, Arqule announced that tivantinib METIV-HCC phase 3 trial for hepatocellular carcinoma is scheduled to conclude in early 2017. Top-line data is expected in the first quarter of 2017.
• On March 22, 2016, ArQule and Daiichi Sankyo announced that the independent data monitoring committee  of the METIV-HCC study conducted the planned interim assessment and it was determined the trial will continue to its final analysis. The interim analysis was triggered when at least 60 percent of the target number of events occurred. The final analysis will take place when 100 percent of the target number of events occurs. The METIV-HCC trial completed patient accrual in December 2015 with more than 300 patients with MET-high HCC enrolled.
• On January 25, 2016, ArQule announced that an analysis of preliminary baseline tumor MET status of patients screened in the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma confirms previously presented data from the company's phase 2 trial in the same patient population. In both trials MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy and was a predictive and prognostic biomarker in the phase 2 trial. The data was presented in an oral presentation and poster at the 2016 Gastrointestinal Cancers Symposium (ASCO GI) on January 22, 2016 .                         The METIV-HCC trial screened patient tumor biopsies for MET status as an inclusion criteria for Met-high patients. Approximately half of the more than 1,000 samples tested were MET-high. A higher MET-high rate (73%) was observed in those samples from patients analyzed following first-line treatment with sorafenib while a lower MET-high rate (39%) was observed in those samples analyzed prior to sorafenib treatment. An additional analysis found that 70% (50 out of 71) of patients who tested MET-low before sorafenib treatment became MET-high after receiving sorafenib.

The METIV-HCC trial, being conducted in western countries in partnership with Daiichi Sankyo, has completed enrollment and a planned interim analysis, which is triggered when 60% of events occur, is expected to take place early in the second quarter of 2016. The trial enrolled over 300 patients, is randomized 2:1 treatment to best supportive care, and has overall survival as its primary end-point.

Is general: Yes