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Xilonix Improves Outcomes in Advanced Colorectal Cancer
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The novel anti-interleukin 1-alpha antibody Xilonix demonstrated significantly improved outcomes compared with placebo in patients with advanced colorectal cancer, according to phase 3 trial data presented at the European Society of Medical Oncology 18th World Congress on Gastrointestinal Cancer. The agent was also shown to be safe and well tolerated in this trial.
Xilonix (XBiotech) is the first monoclonal antibody immunotherapy that specifically targets and neutralizes interleukin-1 alpha (IL-1), “a potent anti-inflammatory signaling molecule known to promote the growth and spread of tumors,” according to a press release. It is the first in a new class of “True Human” therapeutic antibodies, which are entirely derived from individuals with natural disease immunity, potentially providing a treatment option without serious side effects associated with other anti-cancer agents.
Tamas Hickish
“In this first-of-its-kind study, not only did treatment with Xilonix demonstrate clinical benefit but it was also very well-tolerated, suggesting Xilonix has the potential to meet the real and urgent need for more effective, less toxic therapies for patients with advanced colorectal cancer," Tamas Hickish, MD, consultant medical oncologist at Dorset Cancer Center, and visiting professor at Bournemouth University, U.K., said in the press release. “In addition, this study provides evidence that novel endpoints based on symptom recovery can serve as a predictor of overall survival benefit and thus may be used to evaluate an anti-tumor agent in this disease.”
Hickish and colleagues performed a double blind clinical trial evaluating 309 patients with metastatic colorectal cancer refractory to standard chemotherapy who showed a high level of symptoms, functional impairment, weight loss and elevated systemic inflammation. They randomly assigned patients to receive Xilonix or placebo plus best supportive care.
Clinical response rate at 8 weeks served as the primary endpoint. This was measured using new criteria — developed in part by the European Medicines Agency Scientific Advice Working Group — for objective response based on control of symptoms associated with poor prognosis for survival, including pain, fatigue, appetite loss and muscle loss. Disease control was also measured using dual-energy X-ray absorptiometry and the standard European Organization for Research and Treatment of Cancer quality of life questionnaire.
Patients treated with Xilonix experienced a 76% relative increase in clinical response rate compared with placebo (33% vs. 19%; P = .0045). Moreover, clinical response rate correlated with overall survival, and among responders in both arms, clinical response was associated with a 2.7-fold increase in overall survival (11.5 months in responders vs. 4.2 months in nonresponders). All patients were eligible to receive Xilonix at 8 weeks, so overall survival was not compared between treatment and placebo groups.
Compared with nonresponders, responders also gained more lean body mass (P < .0007), had reduced pain and fatigue (P < .001), improved appetite (all P < .001) and improved control of thrombocytosis (P < .0002) and systemic inflammation (P < .0007).
Finally, Xilonix therapy was associated with a “notable lack of toxicity,” and the most common adverse events included abdominal pain, peripheral edema, fatigue, anemia, constipation, weight loss, asthenia, decreased appetite and nausea. Most were mild to moderate, appeared related to the underlying disease, and were similarly prevalent between study arms. There was a 26% relative risk reduction of serious adverse events in the treatment arm compared with placebo (P = .062), but the study was not powered to adequately demonstrate this difference.
The researchers concluded that these data “provide unequivocal evidence that anti-IL-1 monotherapy can serve as a new treatment for advanced [metastatic colorectal cancer.]”
Xilonix is currently being evaluated for advanced colorectal cancer in phase 3 clinical trials in the U.S. with a fast track designation by the FDA. Phase 3 trials have been completed in Europe, and Xilonix is under accelerated review after the EMA validates its market authorization application, with an approval decision expected as early as the fourth quarter of 2016, according to the press release. – by Adam Leitenberger
Reference:
Hickish T, et al. Abstract #O-027. Presented at: European Society of Medical Oncology World Congress on Gastrointestinal Cancer; June 29-July 2, 2016; Barcelona, Spain.
Disclosures: Healio Gastroenterology was unable to confirm relevant financial disclosures at the time of publication.