FIGURE 1 from Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit

Validation of IRS to stratify anti-PD-(L)1 monotherapy benefit in patients with advanced solid tumors. A, Clinical characteristics of the anti-PD-(L)1 monotherapy validation cohort are shown in an alluvial diagram. All patients with available clinical molecular profiling data necessary for IRS (TMB and normalized expression of PD-1, PD-L1, ADAM12, and TOP2A from in-parallel qTP) from FFPE tumor tissue enrolled in the Strata Trial (NCT03061305) and treated with systemic anti-PD-(L)1 monotherapy were considered. Patients in previous IRS discovery or validation were excluded. The locked IRS model and thresholds were used to assign IRS-L (light blue) or IRS-H (increased benefit; dark blue) status. For the 352 eligible patients, IRS status, MSI/TMB status (MSI-H or TMB-H as MSI/TMB-H), type of anti-PD-(L)1 therapy [pembrolizumab (pembro) vs. other anti-PD-(L)1], systemic line of anti-PD-(L)1 therapy, and tumor type [all tumor types with >15 samples considered individually: NSCLC, cancer of unknown primary (CUP), bladder cancer (Blad.), melanoma (Mel.), head and neck cancer (H&N), and EGC; remaining 25 other tumor types considered together] are shown. Stratum are colored by IRS status. IRS stratifies anti-PD-(L)1 monotherapy clinical benefit by rwPFS (by time to next therapy; B) and OS (C). B, Anti-PD-(L)1 monotherapy rwPFS stratified by IRS group is shown by unadjusted Kaplan–Meier analysis, with the aHR [adjusted for age, sex assigned at birth, line of therapy, tumor type and anti-PD-(L)1 therapy type], 95% CI and P value for IRS status (IRS-H vs. IRS-L) shown. The number (n) of patients, events, and median rwPFS (with 95% CI) for each group are shown. Forest plot analyses of rwPFS by IRS status in key subgroups are shown below (Remaining 4 = Blad., Mel., H&N, and EGC). Significant associations are shown by filled in aHR estimates. C, As in B, except assessing OS.