Colorectal Cancer Global Phase III Study

A Global Phase III study for treatment of advanced colorectal cancer patients under U.S. FDA regulatory guidance completed enrollment in December 2016. The study, which received Fast Track designation by the U.S. FDA, evaluated the Company’s lead product candidate for the treatment effect on overall survival in colorectal patients.

Survival analyses are to be performed after 276 (50%), 414 (75%) and 552 (100%) events at the respective stages. The study may be stopped for efficacy or futility at either of the interim analyses, patients are otherwise followed for up to 18 months in order to determine overall survival. The study is powered for 552 events at conclusion.

In February 2017, an Independent Data Monitoring Committee (IDMC) performed a prospectively planned, unblinded analysis of the Phase 3 study data and reported no safety concerns and that indications of efficacy were sufficient to recommend proceeding with the study without modification. This was the first of two interim efficacy analyses planned prior to a final analysis for overall survival. In June 2017, the IDMC performed the second prospectively planned, unblinded analysis and reported no safety concerns. However, the committee recommended the early termination of the study since the findings were not sufficient to meet efficacy or the threshold for continuation, which involved a prospectively defined acceptance boundary for the interim analysis of less than or equal to p=0.08. The Company plans to analyze the data extensively to further understand the primary and secondary endpoint data, as well as to identify populations that may have benefited from the therapy.

Patients enrolled in the XCITE study were randomized 2:1 to receive Xilonix or placebo plus, in each case, best supportive care. Advanced colorectal cancer patients were required to have previous failed regimens that included flouropyrimidines, oxaliplatin, irinotecan, and Cetuximab (or Panitumumab for patients with KRAS mutation). Patients were expected to continue in the study until there was evidence of radiographic progression. The patients were to be followed for up to 18 months in order to determine overall survival. The primary endpoint of this study was overall survival, with secondary endpoints including objective response rate, progression free survival, change in lean body mass and patient reported quality of life measures.