Fig. 1: INSPIRE patient stratification by early ΔctDNA and ΔTM.

A Overview of change of tumor measurement (ΔTM) at best response of all patients enrolled in the INSPIRE clinical trial (n = 106). Patients are grouped by cancer cohort and sorted in order of decreasing ΔTM. Below the waterfall plot, widths of joining lines reflect the number of patients within the corresponding tumor cohort and best overall response by RECIST. B Simplified consort diagram summarizing the number of patients with complete ΔTM, ΔctDNA, and baseline WES profiling stratified into the four pembrolizumab sensitivity groups. LS low-sensitivity, MSER mixed-sensitivity with emerging resistance, MSPP mixed-sensitivity with potential pseudoprogression, HS high-sensitivity. C Distribution of ΔTM and ΔctDNA for each patient. Contours around each group indicate the density within each group with the median shown as the center of the contour. Points are colored according to pembrolizumab sensitivity groups. Dotted red vertical and horizontal lines indicate ΔTM = 0 and ΔctDNA = 0. D Kaplan–Meier plot of overall survival from treatment cycle 3 in patients grouped by pembrolizumab sensitivity. (p = 0.00025). E Kaplan–Meier plot of progression-free survival from treatment cycle 3 in patients grouped by pembrolizumab sensitivity. (p = 8.7 × 10⁻¹¹) F Comparison of TMB distribution between pembrolizumab sensitivity groups. The median for each group is shown as a horizontal line and data points are shown ordered by increasing value. The distance between the third-quartile (Q3) and first-quartile (Q1), known as the interquartile range (IQR), is marked around the median by a black rectangle. Vertical lines extending from the top and bottom of the rectangle show the maximum (Q3 + 1.5-times IQR) and minimum(Q1 + 1.5-times IQR). P-values shown are calculated by a two-sided Kolmogorov–Smirnov test. F Kaplan–Meier plot for overall survival from treatment cycle 3 in patients stratified by TMB ≥ 10 and ΔctDNA. (p = 0.0042). G Kaplan–Meier plot for overall survival from treatment cycle 3 in patients stratified by TMB ≥ 10 and ΔctDNA. (p = 0.0053). P-values for Kaplan–Meier plots reflect the outcomes of log-rank tests for the survival model. H Kaplan–Meier plot for progression-free survival from treatment cycle 3 in patients stratified by TMB ≥ 10 and ΔctDNA. (p = 0.00018). P-values for Kaplan–Meier plots reflect the outcomes of log-rank tests for the survival model. Statistical significance for all panels: ***p ≤ 0.001; **p ≤ 0.01; *p ≤ 0.05; +p ≤ 0.10. Source data are provided in SourceData_Fig1.xlsx.