Tebentafusp induced a pharmacodynamic response in multiple peripheral immune markers and increased CD3+, CD8+, or CD4+ cells in the TME. (A) Maximal postdose (log2) fold change, relative to baseline concentration, in response to first dose in serum markers (n = 41). (B) Temporal profile of post first and third dose fold-change response 12-24 hours following first dose (D1) versus third dose (D15); data points represent mean ± SEM, N = 42. (C) Temporal profile of blood lymphocytes post first and third dose expressed as a fold change from baseline. Data points represent mean ± SEM, n = 32. (D) Number of CD3+, CD8+, or CD4+ cells per mm2 tumor in paired pretreatment and on-treatment biopsies (taken cycle 1 day 16) from up to six patients; line per patient. (E) Representative immunohistochemistry images from patient 2 in (D) from pretreatment and on-treatment biopsies for CD3+ (total T cells), CD4+ (T cells and monocytes), and CD8+ cells (T cells and NK cell subset). HGF, hepatocyte growth factor; IFN, interferon; IL, interleukin; NK, natural killer; TME, tumor microenvironment; TNF, tumor necrosis factor.