Data from PD-1<sup>T</sup> TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC

Abstract

<div>AbstractPurpose:<p>Durable clinical benefit to PD-1 blockade in non–small cell lung cancer (NSCLC) is currently limited to a small fraction of patients, underlining the need for predictive biomarkers. We recently identified a tumor-reactive tumor-infiltrating T lymphocyte (TIL) pool, termed PD-1<sup>T</sup> TILs, with predictive potential in NSCLC. Here, we examined PD-1<sup>T</sup> TILs as biomarker in NSCLC.</p>Experimental Design:<p>PD-1<sup>T</sup> TILs were digitally quantified in 120 baseline samples from advanced NSCLC patients treated with PD-1 blockade. Primary outcome was disease control (DC) at 6 months. Secondary outcomes were DC at 12 months and survival. Exploratory analyses addressed the impact of lesion-specific responses, tissue sample properties, and combination with other biomarkers on the predictive value of PD-1<sup>T</sup> TILs.</p>Results:<p>PD-1<sup>T</sup> TILs as a biomarker reached 77% sensitivity and 67% specificity at 6 months, and 93% and 65% at 12 months, respectively. Particularly, a patient group without clinical benefit was reliably identified, indicated by a high negative predictive value (NPV) (88% at 6 months, 98% at 12 months). High PD-1<sup>T</sup> TILs related to significantly longer progression-free (HR 0.39, 95% CI, 0.24–0.63, <i>P</i> < 0.0001) and overall survival (HR 0.46, 95% CI, 0.28–0.76, <i>P</i> < 0.01). Predictive performance was increased when lesion-specific responses and samples obtained immediately before treatment were assessed. Notably, the predictive performance of PD-1<sup>T</sup> TILs was superior to PD-L1 and tertiary lymphoid structures in the same cohort.</p>Conclusions:<p>This study established PD-1<sup>T</sup> TILs as predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC. Most importantly, the high NPV demonstrates an accurate identification of a patient group without benefit.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-2277" target="_blank">See related commentary by Anagnostou and Luke, p. 4835</a></i></p></div>