A first-of-its-kind monoclonal antibody, termed Xilonix, has been developed to specifically target interleukin-1 alpha (IL-1α). A key and potent inflammatory cytokine produced in the body, IL-1α is overexpressed by tumor cells as a tumor grows and develops. In a recent Phase III study, researchers have used this novel anti-IL-1α antibody to tackle advanced colorectal cancer.
Presenting their data at the European Society for Medical Oncology’s (ESMO’s) 18th World Congress of Gastrointestinal Cancer in (29 June – 2 July, Barcelona, Spain), lead investigator Tamas Hickish (Royal Bournemouth Hospital NHS Foundation Trust, Bournemouth, UK) stated: “IL-1α in tumors promotes angiogenesis, helping to provide crucial blood supply for tumor growth, and it can also send the body’s metabolism out of control, causing it to burn muscle and lose weight,”
In this Phase III trial, 309 patients with metastatic colorectal cancer that was unresponsive to standard chemotherapy of oxaliplatin and irinotecan were enrolled. The patients also presented with a high degree of symptoms; functional impairment; weight loss; or elevated systemic inflammation.
Alongside trialing the new agent, Hickish and colleagues collaborated with the European Medicines Agency’s Scientific Advice working group to implement new criteria for objective response built around the control of symptoms. Dual-energy X-ray absorptiometry and EORTC-QLQC30 were used in order to evaluate disease control in conjunction with these criteria.
Patients were randomized in a 2:1 ratio to treatment with either MABp1 with best supportive care, or placebo with best supportive care.
Patients treated with Xilonix displayed a significant 76% relative increase in their clinical response rate compared with those in the placebo arm. Responding patients lived almost three times as long as those that had no response to treatment (11.5 months vs 4.2 months, respectively). Treated patients also reported 25% less serious adverse events than those in the placebo control group.
The team also discovered that alongside improved health status, improvement in nearly all other self-reported and laboratory-based measures were reported, such as improved control of white blood cell activity in relation to the tumor and reduced systemic inflammation overall.
“These data suggest Xilonix is very well tolerated, and has the potential to meet the real and urgent need for more effective, less toxic therapies for patients with advanced colorectal cancer. This study also provides the first evidence that health status can actually be used to measure efficacy of antitumor therapy in advanced, refractory colorectal cancer, and that clinical responses based on health status can be a predictor of overall survival benefit,” Hickish concludes.