Interleukin-1 receptor antagonist levels predict favorable outcome after bermekimab, a first-in-class true human interleukin-1α antibody, in a phase III randomized study of advanced colorectal cancer
Authors: Kurzrock, R., Hickish, T., Wyrwicz, L., Saunders, M., Wu, Q., Stecher, M., Mohanty, P., Dinarello, C.A. and Simard, J.
Journal: OncoImmunology
Volume: 8
Issue: 3
eISSN: 2162-402X
ISSN: 2162-4011
DOI: 10.1080/2162402X.2018.1551651
Abstract:Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.
Source: Scopus
Interleukin-1 receptor antagonist levels predict favorable outcome after bermekimab, a first-in-class true human interleukin-1α antibody, in a phase III randomized study of advanced colorectal cancer.
Authors: Kurzrock, R., Hickish, T., Wyrwicz, L., Saunders, M., Wu, Q., Stecher, M., Mohanty, P., Dinarello, C.A. and Simard, J.
Journal: Oncoimmunology
Volume: 8
Issue: 3
Pages: 1551651
ISSN: 2162-4011
DOI: 10.1080/2162402X.2018.1551651
Abstract:Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.
Source: PubMed
Interleukin-1 receptor antagonist levels predict favorable outcome after bermekimab, a first-in-class true human interleukin-1α antibody, in a phase III randomized study of advanced colorectal cancer
Authors: Kurzrock, R., Hickish, T., Wyrwicz, L., Saunders, M., Wu, Q., Stecher, M., Mohanty, P., Dinarello, C.A. and Simard, J.
Journal: ONCOIMMUNOLOGY
Volume: 8
Issue: 3
ISSN: 2162-402X
DOI: 10.1080/2162402X.2018.1551651
Source: Web of Science (Lite)
Interleukin-1 receptor antagonist levels predict favorable outcome after bermekimab, a first-in-class true human interleukin-1α antibody, in a phase III randomized study of advanced colorectal cancer.
Authors: Kurzrock, R., Hickish, T., Wyrwicz, L., Saunders, M., Wu, Q., Stecher, M., Mohanty, P., Dinarello, C.A. and Simard, J.
Journal: Oncoimmunology
Volume: 8
Issue: 3
Pages: 1551651
eISSN: 2162-402X
ISSN: 2162-4011
DOI: 10.1080/2162402x.2018.1551651
Abstract:Bermekimab is a true human monoclonal antibody that targets interleukin-1alpa (IL-1α), an inflammation-mediating alarmin. IL-1 receptor antagonist (IL-1Ra) is a natural molecule that blocks IL-1α activity by occupying the IL-1 receptor. The effect of endogenous IL-1Ra levels on the effectiveness of bermekimab is unknown. We investigated whether pre-treatment levels of circulating IL-1Ra, assessed by an enzyme-linked immunoassay, correlated with achievement of the primary outcome endpoint (effect on lean body mass and symptoms at week 8) in a Phase III study (2:1 randomization) of bermekimab versus placebo (each with best supportive care) in advanced colorectal cancer. Patients who responded to bermekimab in terms of achieving the primary endpoint had lower levels of IL-1Ra than non-responders (N = 204 patients; median = 843 vs. 1035 pg/ml, p=0.0092); no such relationship was observed in the placebo arm (N = 100 patients; 901 vs. 984 pg/ml, p = 0.55). Multivariate analysis corroborated that, in the bermekimab group, patients with lower baseline IL-1Ra levels were more likely to achieve the primary endpoint (odds ratio (OR) 1.7 (95% confidence interval (CI), 1.1 to 2.6), p = 0.017); in contrast, in the placebo arm, pre-treatment plasma IL-1Ra levels were not associated with outcome (OR 1.2 (95% CI 0.6 to 2.5), p = 0.57). The current findings demonstrate that, in a randomized phase III trial, patients with advanced colorectal cancer and lower levels of circulating IL-1Ra are more responsive to treatment with the IL-1α-targeting antibody bermekimab and these observations define a potential biomarker for anti-IL-1α therapy.
Source: Europe PubMed Central