Abstract 6725: AI-derived H&E biomarkers predict differential survival under immunotherapy vs chemotherapy in phase-3 metastatic NSCLC study NEPTUNE.

Abstract Background: Immunotherapy outcomes in metastatic NSCLC are variable, and existing biomarkers (PD-L1, TMB) incompletely predict benefit. Routine H CTX n=272) were processed using models trained independently on external, non-NEPTUNE datasets (6, 000 pathologist-annotated H bTMB ≤20 mut/Mb) as described in the NEPTUNE study (de Castro Jr G et al. , J Thorac Oncol, 2023;18: 106-119). Results: Higher stromal fibroblast density was associated with inferior OS in both arms (D+T HR=1. 60 1. 14-2. 25; CTX HR=1. 36 1. 05-1. 76) with no treatment interaction (nominal pᵢnteraction=0. 82), indicating a prognostic effect. Higher stromal immune density was associated with improved benefit for D+T (HR=0. 64 0. 45-0. 90; median OS difference +5. 8 months; FDR p=0. 04) but not CTX (HR=0. 84 0. 65-1. 08, FDR p=0. 38), with a significant treatment interaction (nominal pᵢnteraction=0. 03), supporting a predictive effect. Overall, AI-H Part 1 (Regular Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (7 Suppl): Abstract nr 6725.