Date: 2017-06-09
Type of
information: Halting of the trial
phase: 3
Announcement: halting of the trial
Company: XBiotech (USA - TX)
Product: Xilonix™
Action
mechanism: monoclonal antibody. Xilonix™ is the first monoclonal antibody to specifically target and neutralize interleukin-1 alpha (IL-1 alpha), one of the most potent inflammatory signaling molecules. The IL-1 pathway in general, and IL-1 alpha in particular, is a desirable target for anti-cancer therapy because of its potential role in both local and systemic effects of cancer. IL-1 alpha in the tumor microenvironment is known to promote angiogenesis as well as mediate symptoms such as metabolic dysregulation, fatigue and anxiety associated with advanced cancer.
Disease: advanced colorectal cancer
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details: The purpose of the XCITE study is to determine if the True Human Monoclonal antibody Xilonix® (MABp1) can prolong the life of colorectal carcinoma patients that are refractory to standard therapy. This double-blind, placebo-controlled Phase III study is randomized 2:1 with patients receiving Xilonix or placebo plus best supportive care. Patients are required to have metastatic colorectal cancer, and are required to have failed regimens that include flouropyrimidines, oxaliplatin, irinotecan, and Cetuximab or Panitumumab for patients with KRAS mutation. Patients continue on study until there is evidence of radiographic progression. The primary endpoint of this study is overall survival, with secondary endpoints including objective response rate, progression free survival, change in lean body mass as measured by dual energy X-ray absorptiometry (DEXA), and patient reported quality of life using the validated EORTC QLQ C30 questionnaire. There are two scheduled interim analyses and a final analysis. The study may be stopped for efficacy at either interim analysis, which would potentially enable an early submission of a request for marketing authorization. Patients are otherwise followed for up to 18 months in order to determine overall survival and the study is powered for 552 events at study conclusion. (NCT01767857)
Latest
news:
- • On June 9, 2017, XBiotech announced that an Independent Data Monitoring Committee (IDMC) has performed its second prospectively planned, unblinded analysis of the Phase 3 XCITE study for Xilonix® (MABp1) for the treatment of colorectal cancer. The IDMC had no safety concerns from the unblinded analysis. 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. XBiotech now 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. The company will pursue its efforts for the approval of the therapy based on the successful completion of the European study, which demonstrated control of debilitating symptoms in colorectal cancer.
- • On February 21, 2017, XBiotech announced that an Independent Data Monitoring Committee (IDMC) has performed a prospectively planned, unblinded analysis of the Phase 3 XCITE study for Xilonix® for colorectal cancer. The IDMC reported that the FDA Fast-Tracked study had no safety concerns and that indications of efficacy were sufficient to recommend proceeding with the study without modification. These findings also lend support to the Company’s recently completed Phase 3 study in Europe, which used a novel primary endpoint to evaluate efficacy for the same antibody therapy for the treatment of advanced colorectal cancer. According to the IDMC charter, this was the first of two interim efficacy analyses planned prior to the final analysis for overall survival.
• On December 7, 2016, XBiotech announced that enrollment has been completed in its randomized, double-blind, placebo-controlled Phase III study evaluating Xilonix® as a treatment for advanced colorectal cancer. The Phase III study is being conducted under Fast Track designation from the FDA and involves over 600 advanced cancer patients from 18 countries world-wide. The Company reports that the first interim analysis allowing an assessment by the Data Monitoring Committee (DMC) of both safety and efficacy is expected as early as first quarter 2017.
- • On July 22, 2016, XBiotech said that the Independent Data Monitoring Committee (DMC) for the XCITE Phase III clinical study of Xilonix® for the treatment of colorectal cancer, recently recommended study continuation without any amendment to the study design. The DMC convened as scheduled, subsequent to the enrollment of 400 patients into the study. The DMC did not have any recommendations for the Company regarding any need for changes to the study operation.
- Another DMC meeting is scheduled to occur either after 600 patients have been enrolled, or potentially earlier if the study meets its first planned efficacy analysis milestone.
- The XCITE study is on schedule to reach its enrollment milestones in 2016. XBiotech’s marketing authorization application for Xilonix® for the treatment of colorectal cancer remains on schedule to achieve a decision in 2016 by the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP). The Company recently scheduled an in-person meeting with the CHMP. The Company believes the meeting will help advance the marketing authorization process and has agreed with the CHMP for the MAA to be reviewed under the standard assessment timetable, rather than the accelerated review timeline that was granted in April 2016. The Company says that the standard timetable will provide additional time to conduct the MAA process. The standard timetable is expected to add approximately 60-days to the review proceedings.
Is
general: Yes
