In this dose-expansion cohort study, we compared 0.24 mg/kg and 1.2 mg/kg dose levels of the 4-1BB/CD137 agonist antibody utomilumab with respect to safety, antitumor activity, pharmacokinetics, and biomarkers in patients with metastatic melanoma and NSCLC. Here, TNFRSF9 is linked to metastatic melanoma.