A first-in-class true human IL1α antibody was well tolerated in patients with metastatic cancer.
Major finding: A first-in-class true human IL1α antibody was well tolerated in patients with metastatic cancer.
Clinical relevance: IL1α neutralization led to a decrease in plasma IL6 levels and increased lean body mass.
Impact: Use of an IL1α blocking antibody may combat pleiotropic effects of inflammation in multiple cancers.
Chronic inflammation is a hallmark of cancer and underlies many aspects of the malignant phenotype, such as tumor progression and cachexia. A suitable therapeutic target for reducing cancer- associated inflammation has proven elusive. Interleukin 1α (IL1α) is an early component of inflammatory responses that may promote cancer-associated inflammation through its expression on platelets and leukocytes. Hong and colleagues conducted an open-label, dose-escalation phase I trial to evaluate MABp1, a true human monoclonal antibody specific for IL1α, in 52 adults with refractory metastatic cancers representing 18 different tumor types. The primary objectives were to assess the safety and tolerability of MABp1, characterize its pharmacokinetic profile, and determine the recommended phase II dose. Secondary objectives included evaluation of antitumor activity and pharmacodynamic effects and assessment of changes in cancer-related cachexia and quality of life. MABp1 was very well tolerated, with relatively few adverse effects and no discontinuations due to MABp1 treatment. MABp1 serum concentrations were consistent at all doses. Of 34 evaluable patients, 10 (29%) had stable disease and 1 (3%) experienced a partial response. Serum levels of IL6 were used as a biomarker of IL1α activity; in 42 patients tested, median plasma concentrations of IL6 decreased, though this result was not statistically significant. Of 30 patients evaluated for changes in cancer-associated cachexia, 21 (70%) gained lean body mass; plasma IL6 levels were significantly decreased in these patients but not in those who lost lean body mass. Quality of life significantly improved among 33 patients assessed. Although further testing with a larger number of patients is necessary to determine how the effects of MABp1 are mediated and the effect of IL1α neutralization on survival, these results indicate that targeting IL1α is feasible and provide support for further clinical evaluation of MABp1.
Hong DS, Hui D, Bruera E, Janku F, Naing A, Falchook GS, et al. MABp1, a first-in-class true human antibody targeting interleukin-1α in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol 2014;15:656–66.
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