Positive results from a phase III trial in advanced colorectal cancer showed that Xilonix-treated patients with advanced disease and multiple symptoms known to inversely correlate with overall survival experienced a 76 percent relative increase in clinical response rate after eight weeks of therapy compared to placebo, at 33 percent vs. 19 percent, respectively (p=.0045).
Clinical response correlated with improved overall survival. Among responders, clinical response was associated with an increase in overall survival, at 11.5 months vs. 4.2 months in responders compared to non-responders, respectively.
Overall survival was not compared between treatment arms, because after eight weeks all patients were eligible to receive Xilonix, a monoclonal IgG1k antibody immunotherapy. Treatment was well tolerated, with an adverse event profile comparable to placebo. The results were presented by XBiotech Inc. at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer.
In addition to increased overall survival, responders gained more lean body mass compared to non-responders (p<0.0007), had reduced fatigue and pain (p<0.001) and improved appetite (p<0.001), according to the XBiotech. Control of thrombocytosis and systemic inflammation were also significantly improved (p<0.0002 and p<0.0007, respectively).
The most common adverse events reported were abdominal pain, peripheral edema, fatigue, anemia, constipation, decrease in weight, asthenia, decreased appetite and nausea. The majority of these events were characterized as mild to moderate and appeared to be related to the underlying disease. The prevalence of AEs was similar in both treatment and placebo groups.
“There is an urgent need for new forms of anti-tumor, disease-modifying cancer therapies that effectively control disease while being less toxic,” said John Simard, founder, president and CEO of XBiotech. “We believe these data demonstrate that our True Human monoclonal antibody targeting interleukin-1 alpha has the potential to meet this critical need.”
In the double-blind study, 309 patients were randomized 2:1 to receive Xilonix plus best supportive care versus placebo plus BSC. Study participants had failed all available chemotherapy and had metastatic disease with one or more symptoms of metabolic dysfunction and functional impairment (i.e., elevated systemic inflammation, unintentional weight loss, pain, fatigue, anorexia). Patients were required to have an Eastern Cooperative Oncology Group function status of only 1 or 2.
CRR was assessed using dual-energy X-ray absorptiometry to determine lean body mass and using the standard European Organization for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) to capture patients’ own assessment of their fatigue, pain and anorexia from baseline to week eight.
To be classified as responders, patients had to maintain or improve LBM and maintain or improve in at least two of the three categories of pain, fatigue and anorexia. Secondary endpoints evaluated paraneoplastic thrombocytosis and systemic inflammation, as well as median overall survival, which compared responders vs. non-responders.
