Fig. 2: Pharmacokinetics and pharmacodynamics.

A Ceralasertib PK. PK samples were taken on the days of PD sampling, pre- and 4–8 h post-dose. Individual points are shown, line = mean, error = 95% confidence interval. B PBMC phospho^(S345)Chk1 immunofluorescence intensity, plotted as fold-change vs. baseline levels, pre-fraction 1 (after 3–7 days ceralasertib dosing) and pre-fraction 2 (after a single fraction of 2 Gy radiation), by dose cohort, line = median, box = interquartile range, whisker = range. n = 3 (20 mg BD), n = 4 (40 mg BD), n = 9 (80 mg BD). C PBMC phospho^(S345)Chk1 immunofluorescence intensity, individual points as shown in (B). Size of points = dose (mg BD), color indicates corresponding pre-dose plasma ceralasertib level, if available (grey: not available). * = P = 0.035 by two-sided Wilcoxon Signed Rank test, versus a theoretical median of 1. Data includes one-sample where pre-F1 and pre-F2 samples were mixed, this has been included in both pre-F1 and pre-F2 columns. Source data for this figure (A–D) are provided online. D γH2AX foci in skin punch biopsies, absolute count of foci per nucleus, median of 765 (range 72–2204) nuclei were quantified per patient per time point, number of nuclear foci per nucleus displayed. * = P = 0.024 by unpaired t-test (two-tailed), comparing pre-F2 to baseline. E Representative micrographs of skin-punch biopsies stained for γH2AX by IHC. Left = baseline; middle = pre-fraction 1; right = pre-fraction 2. Scale bar = 50 μm. F Tumor pharmacodynamics in paired tumor biopsies before treatment and prior to fraction 2. Left: change in γH2AX % positivity; right: change in phospho^(S635)Rad50 % positivity. G Example micrographs for the tumor biopsies quantified in (G). Scale bar = 100 μm.