ARQL
Can they even get a good tx dose at 120 MG BID ???
Item 8.01 Other Events.
ArQule, Inc. (“ArQule” or the “Company”) and its partner, Daiichi Sankyo, Inc. (“Daiichi Sankyo”) are currently sponsoring a Phase 3 trial of tivantinib in the treatment of hepatocellular cancer (“HCC”). This trial is known as the METIV-HCC study. Recently the Company and Daiichi Sankyo received a letter from the trial Data Monitoring Committee (“DMC”) recommending that the study dosage be reduced from 240 mg twice daily (“BID”) to 120 mg BID and that certain enhanced patient monitoring procedures be instituted to confirm the safety profile of the lower dose. This recommendation resulted from the observation of a higher incidence of neutropenia in the METIV-HCC trial than was observed in the Company’s and Daiichi Sankyo’s Phase 2 trial in the same patient population.
The Company and Daiichi Sankyo have accepted the recommendation of the DMC to implement the lower dose and will be filing a protocol amendment with regulatory authorities and related parties. After a prescribed number of patients have been dosed at 120 mg BID, the DMC will review data from that patient cohort to determine the safety profile of the lower dose and whether to recommend any further action. Because the trial is still in the early stages of recruitment, the Company and Daiichi Sankyo are not able to comment at this time on whether the timeline for recruitment of the trial may be delayed compared with original estimates as a result of the proposed amendment and subsequent data review.
The Company and Daiichi Sankyo expect that the dose reduction will reduce the incidence of neutropenia observed to date in the METIV-HCC trial, resulting in greater patient safety and fewer early patient terminations. The Companies also believe they have now selected a dose that will offer the best possibility for a favorable benefit-risk ratio.
The Company and Daiichi Sankyo will continue to review available data from this and other studies to better understand the increased incidence of neutropenia observed in the METIV-HCC trial compared with the Phase 2 HCC trial, including any possible impact from a change in dosage form. The incidence of neutropenia seen in the METIV-HCC trial to date has not been observed in other trials with tivantinib, which continue to employ a dose of 360 mg BID.
The METIV-HCC trial is a randomized, double-blinded study of tivantinib as single agent therapy in previously treated patients with MET diagnostic-high inoperable HCC. It is being conducted under a Special Protocol Assessment with the FDA. The primary endpoint of the study is overall survival in the intent-to-treat population, and the secondary endpoint is progression free survival in the same population.
