Fig. 2.

Pharmacodynamic effects of oleclumab in tumor tissue. a Decrease in CD73 enzymatic activity 20 days after treatment initiation as demonstrated by an in situ enzymatic assay. Patient 4 had no tumor cell CD73 expression or enzymatic activity at baseline but had CD73 enzymatic activity in adjacent liver tissue prior to treatment that decreased following treatment. Representative images are shown at 20X magnification. With this method, enzymatic activity leads to a brown coloring. Patients with CRC or PDAC were treated with oleclumab monotherapy and their tumors were assessed for CD73 and CD8 expression. b Change of 2+ /3+ CD73 staining in tumor cells from screening to 20 days after oleclumab initiation. c Change of 2+ /3+ CD73 staining in tumor cells from screening to 20 days after treatment initiation by oleclumab dose. d Quantification of total CD8+ cells/mm² at screening and 20 days after oleclumab treatment and e correlation of the fold change in CD8+ cells with the fold change in the percentage of 2+ /3+ CD73+ tumor cells 20 days after treatment initiation. Panels b-e show patients who had baseline CD73 expression of ≥ 10% on tumor cells. In panels b and d, red lines represent patients who had ≥ twofold decreases from screening in CD73 levels. In panels b, c, and d, filled symbols (and solid lines in panels b and d) represent patients with CRC and open symbols (and dashed lines in panels b and d) represent patients with PDAC. CD73 cluster of differentiation 73, CRC colorectal cancer, L liver, LLOQ lower limit of quantitation, PDAC pancreatic ductal adenocarcinoma, T tumor, TILs tumor infiltrating lymphocytes