The F16IL2 immunocytokine and its ECM target TnC-A1, F16IL2 pharmacokinetics, and body temperature changes after F16IL2 and BI 836858 administration. (A) The F16 antibody fragment is composed of variable regions of human heavy and light immunoglobulin chains (VH and VL), bound into a single polypeptide chain by a flexible 5-amino-acid linker (diabody format). Two molecules of human IL-2 are fused to the C terminus of each light chain. (B) The F16 antibody selectively targets the alternatively spliced A1 domain of tenascin-C (TnC-A1), which is spliced into the TnC molecule during angiogenesis and tissue remodeling. (C-D) Pharmacokinetic F16IL2 concentration/time curves in the serum of patients from cohorts 1 and 2 vs cohorts 3 and 4. Data are presented as mean ± standard error of the mean (SEM) on a linear (C) and a logarithmic (D) scale. Three patients were excluded: UPN004 (anomalous low values caused by technical problems), UPN006 (insufficient PK sampling), and UPN901 (stability issue with serum samples). (E) Acute body temperature changes after infusion of F16IL2 on day 1 and BI 836858 on day 3. Fevers were the most frequent treatment-related AEs in the study and body temperature elevations were predominantly observed within hours after the first administration of F16IL2.