Phase III trial finds excellent safety and tolerability
BARCELONA-LUGANO, 02 July 2016 – A novel anti-interleukin 1-alpha antibody has shown a significant impact on symptoms, and a high level of safety and tolerability in patients with advanced colorectal cancer, according to phase III data (1) presented at the European Society for Medical Oncology’s 18th World Congress of Gastrointestinal Cancer in Barcelona, Spain.
Xilonix is the first monoclonal antibody immunotherapy to specifically target and neutralize interleukin-1 alpha (IL-1α), one of the most potent inflammatory substances manufactured by the body or tumour cells.
“IL-1α in tumours promotes angiogenesis, helping to provide crucial blood supply for tumour growth, and it can also send the body’s metabolism out of control, causing it to burn muscle and lose weight,” said lead investigator Dr Tamas Hickish. At the same time, IL-1α effects on the brain can cause the fatigue, anxiety and anorexia associated with advanced cancer.
The study enrolled 309 patients with metastatic colorectal cancer whose disease had not responded to standard chemotherapy with oxaliplatin and irinotecan and who showed a high degree of symptoms, functional impairment, weight loss or elevated systemic inflammation.
In addition to trialing the new agent, researchers also implemented new criteria for objective response based on control of symptoms, which were developed in collaboration with the European Medicines Agency’ Scientific Advice Working Group. These criteria were applied in conjunction with dual-energy X-ray absorptiometry and EORTC-QLQC30 to assess disease control.
Patients were randomized them in a 2:1 ratio to MABp1 with best supportive care, or placebo and the same.
Treatment with MABp1 was associated with a significant 76% relative increase in clinical response rate. Patients who showed a clinical response lived almost three times as long as those who did not respond (11.5 months vs. 4.2 months).
Researchers also found that measures of improved health status correlated with improvement in almost all other self-reported and laboratory-based measures of health, including with improved control of tumor-related white blood cell activity and reduced systemic inflammation.
There were also one-quarter fewer serious adverse events in the treatment arm of the study compared to placebo.
“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,” Dr Hickish said.
“This study also provides the first evidence that health status can actually be used to measure efficacy of anti-tumour therapy in advanced, refractory colorectal cancer, and that clinical responses based on health status can be a predictor of overall survival benefit.”
Notes to Editors
References
1 Abstract O-027 - ‘A pivotal phase 3 Trial of MABp1 in advanced colorectal cancer’ will be presented by dr. Tamas Hickish during Session XIX: Colorectal Cancer, on Saturday, 2 July 2016, 11:15 AM (CEST).
Disclaimer
Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.
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O-027
A pivotal phase 3 trial of MABp1 in advanced colorectal cancer
Hickish Tamas1, André Thierry2, Wyrwicz Lucjan3, Saunders Mark4, Sarosiek Tomasz5, Nemecek Radim6, Kocsis Judit7, Stecher Mike8, de Gramont Aimery9
1Oncology Department, Royal Bournemouth Hospital NHS Foundation Trust, Bournemouth, United Kingdom, 2Saint Antoine Hospital, Paris, France, 3M Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland, 4Christie Hospital NHS Foundation Trust, Manchester, United Kingdom, 5Magodent, Warsaw, Poland, 6Masaryk Memorial Cancer Institute, Brno, Czech Republic, 7University of Debrecen, Debrecen, Hungary, 8XBiotech USA, Inc., Austin, Texas, 9Oncology Department, Institut Hospitalier Franco-Britannique, Levallois-Perret, France
Introduction: The incidence of colorectal cancer (CRC) is associated with economic development and is the second leading cause of cancer in the industrialized world. At least half of patients diagnosed will progress and succumb to the disease. Consequently, a substantial and growing unmet need exists for a therapy to treat patients with advanced CRC. We evaluated a novel anti-IL-1 alpha antibody therapy in patients with advanced disease and multiple symptoms known to inversely correlate with overall survival. OR criteria were developed in collaboration with EMA’s Scientific Advice Working Group to assess anti-tumor benefit of therapy based on control of these symptoms.
Methods: 309 patients were randomized 2:1 to receive MABp1 plus best supportive care (BSC) versus placebo plus BSC. Patients had metastatic colorectal cancer refractory to standard chemotherapy including oxaliplatin and irinotecan. Inclusion criteria also required a constellation of symptoms/functional impairment (ie. pain, fatigue, anorexia, ECOG 1 or 2), weight loss or elevated systemic inflammation.
Objective response criteria used dual-energy X-ray absorptiometry and EORTC-QLQC30 to assess disease control. Secondary endpoints were pharmacodynamics measures also known to correlate with survival. Data was also reported on incidence of Serious Adverse Events (SAEs) and disease progression. Patients were prohibited from receiving any agents that could affect the outcome, including chemotherapy or steroids.
Results: Primary endpoint analysis was performed on 102 placebo and 207 MABp1 patients using a non-parametric statistical test. A 33% treatment response compared to versus 19% for placebo was significant (p=0.0045). Secondary endpoints were also significant, with improved control of paraneoplastic thrombocytosis and reduced systemic inflammation (IL-6) in treated patients versus placebo (p=0.003 and p=0.004 respectively). Safety and tolerability was excellent as evidenced by a 26% relative risk reduction in the number of SAEs in the treatment arm compared to placebo (p=0.062).
Conclusion: A novel symptom-based OR a criterion was used successfully to assess efficacy of a new anti-cancer agent. These findings provide unequivocal evidence that anti-IL-1alpha monotherapy can serve as a new treatment for advanced mCRC. [NCT02138422]