Phase III trial of Xilonix (monoclonal antibody) reports reduction in serious adverse events in colorectal cancer patients- XBiotech

XBiotech has completed data analysis for its Phase III European study of Xilonix (monoclonal antibody) in the treatment of advanced, symptomatic colorectal cancer. In addition to previously announced positive results regarding the primary endpoint of the pivotal study, complete data analysis further demonstrated that key secondary measures of antibody activity were also improved. Inhibition of IL-1 alpha on the surface of platelets may represent an important anti-tumor, disease-modifying activity, due to the mechanism of action of Xilonix.

In the study, median platelet counts among placebo patients were found to be increased 5-fold compared to patients who received Xilonix, whose platelet counts remained near baseline levels during the treatment cycle. Furthermore, while the study was not powered to demonstrate differences in serious adverse events between treatment and placebo groups, there was a 26% reduction in the risk of SAEs in the treatment arm relative to placebo. A treatment-related reduction in SAEs compared to placebo patients is a remarkable and important finding. This may be the first report of a placebo controlled, randomized clinical study of an anticancer agent where there was reduced incidence of SAEs in a treatment arm. Finally, patients in the treatment arm were found to be 53% more likely to have stable disease compared to placebo at eight weeks. The trends toward reduced disease progression and a reduction in SAEs is compelling given the small patient population in the study.

Comment: The company has previously reported issues with the number of patients in its Phase III trial. Data cleaning revealed a fewer number of per protocol patients available for primary endpoint evaluation and 25 patients dropped off prior to receiving any dosing with drug or placebo. Analysis of patient blood samples also revealed that 14 patients erroneously received either placebo or study drug. In addition, 33 patients completed the study but failed to receive scheduled DEXA scans, properly complete EORTC evaluation, or both. The Company reports that these combined irregularities compromised data from 72 patients. With the loss of an additional patients, the study will have reduced statistical power to demonstrate the proposed effect.