FIGURE 2 from Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit
Authors: Bulen Benjamin J. , Khazanov Nickolay A. , Hovelson Daniel H. , Lamb Laura E. , Matrana Marc , Burkard Mark E. , Yang Eddy Shih-Hsin , Edenfield William J. , Claire Dees Elizabeth , Onitilo Adedayo A. , Buchschacher Gary L. , Miller Alan M. , Parsons Benjamin M. , Wassenaar Timothy R. , Suga Jennifer M. , Siegel Robert D. , Irvin William , Nair Suresh , Slim Jennifer N. , Misleh Jamal , Khatri Jamil , Masters Gregory A. , Thomas Sachdev , Safa Malek M. , Anderson Daniel M. , Mowers Jonathan , Dusenbery Anna C. , Drewery Stephanie , Plouffe Komal , Reeder Travis , Vakil Hana , Patrias Lynnae , Falzetta Amanda , Hamilton Ryan , Kwiatkowski Kat , Johnson D. Bryan , Rhodes Daniel R. , Tomlins Scott A. 
Published: July 2023

<p>Confirmation of the added utility of the IRS versus clinical PD-L1 IHC and TMB alone. <b>A,</b> Normalized PD-L1 (<i>CD274</i>) expression (and the other IRS expression components) by the qTP platform used to generate IRS were validated versus qRT-PCR in a validation cohort of 96 FFPE tumor tissue samples tested by clinical CGP and in parallel qTP. The Pearson correlation and linear range of each component is shown (<a href="#SMF1" target="_blank">Supplementary Fig. S1</a>). <b>B</b> and <b>C</b>, The Pearson correlation of normalized <i>PD-L1</i> expression by qTP [log<sub>2</sub> normalized reads per million (nRPM) units] versus clinical PD-L1 IHC score (in submitted pathology reports) was determined in two cohorts of clinical FFPE tumor tissues [regardless of TMB availability and anti-PD-(L)1 treatment]. <b>B,</b> PD-L1 expression by qTP (log<sub>2</sub> normalized units) versus PD-L1 IHC by TPS [using the 22C3 antibody clone (log<sub>2</sub> TPS) in 276 clinically tested FFPE NSCLC tumors with available TPS is plotted]. The linear fit, Pearson correlation (<i>r</i>), and <i>P</i> value are shown. <b>C,</b> PD-L1 expression by qTP versus PD-L1 IHC by CPS using the 22C3 antibody clone (log<sub>2</sub> CPS) in 221 clinically tested FFPE tumors (23 tumor types; most frequently EGC) with available TPS is plotted. The linear fit, Pearson correlation (<i>r</i>), and <i>P</i> value are shown. <b>D,</b> Using B and C, we identified a cohort of all 189 eligible NCT03061305 patients with IRS and PD-(L)1 IHC in accompanying pathology reports who were treated with anti-PD-(L)1 therapy (± chemotherapy). The association of biomarkers with anti-PD-(L)1 rwPFS was determined by Cox proportional hazards modeling [adjusting for age, sex assigned at birth, line of therapy, tumor type, therapy type (monotherapy vs. chemotherapy combination), and inclusion in IRS discovery status]. PD-L1 IHC score (continuous; log<sub>2</sub>) was included in the baseline model (Model 1), with the aHR, 95% CI, number (<i>n</i>) of patients and events, and <i>P</i> value shown for the biomarker term by forest plot. TMB status (-H vs. -L; pink) and IRS status (-H vs. -L; light blue) were separately added to this model (Models 2 and 3, respectively). The significance of each biomarker term is shown and the <i>P</i> value of the LRT comparing the full (Model 2 or 3) versus reduced (Model 1) model is shown. Model 4 includes PD-L1 IHC, TMB, and IRS. Significant biomarker terms are shown by filled in aHR estimates. <b>E,</b> Anti-PD-(L)1 rwPFS stratified by IRS group is shown by unadjusted Kaplan–Meier analysis, with the aHR from Model 4 in D shown. See <a href="#SMT7" target="_blank">Supplementary Table S7</a> for full subgroup analysis.</p>