Utomilumab in Refractory Melanoma and NSCLC (NCT01307267)

The paper reports clinical and translational results from patients with non-small-cell lung cancer (NSCLC) or melanoma dosed once every 4 weeks with either 0.24 mg/kg or 1.2 mg/kg of single-agent utomilumab, a 4-1BB/CD137 agonist mAb. The dose levels tested were well-tolerated but clinical efficacy was low. Analysis of gene expression in tumor biopsies suggested utomilumab efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity may be reduced at higher doses. In vitro models of stimulated human T cells showed loss of pharmacodynamic activity at higher doses of utomilumab. Tumor biopsies collected either before or after utomilumab treatment were subjected to RNA-seq analysis