Abstract 7766: Single-dose neoadjuvant atezolizumab in resectable stage IA-IIIA non-N2 NSCLC: Tumor infiltrate analysis from the PRINCEPS trial

Abstract Phase 2 PRINCEPS trial (NCT02994576) showed that single dose neoadjuvant Atezolizumab (A, 1200 mg IV) was feasible in 30 stage IA-IIIA non-N2 NSCLC patients (treated arm, T). A comparative arm (C) was later added. We report tumor immune profiles and updated survival for T and C arms. C arm included untreated resected stage IA-IIIA non-N2 NSCLC patients. Surgery samples were profiled for residual viable tumor (RVT) and immune infiltrates. RVT cutoffs were defined with Maximally Selected Rank Test for DFS/OS (Table1). Immune infiltrates (N=316) were compared across groups by Mann Whitney U test. From 9/2019 to 8/2022, 30 patients were enrolled in C (2 non-NSCLC excluded). Mean age was 64 vs 66, squamous histology 13% vs 26%, PD-L1 neg 63% vs 46%, adjuvant ChT 20% vs 50% (T vs C). T arm tumors were enriched in CD45+ leukocytes, CD8+ T cells, HLA-DR+ CD163+ myeloids; C arm tumors showed CD115+ CD163+ macrophages and CD16Low immature neutrophils suggesting an immunosuppressive TME. In T arm, Responders (RVT≤60%) had higher lymphocyte, activated/exhausted PD-1+/TIGIT+ T cell and mature/activated CD16+ CD11bHigh neutrophil rates; Non-Responders (RVT>60%) showed more senescent CD57+ T cells and immunosuppressive (CD16-, CD163+) myeloids. In C arm, Spontaneous Regressors (RVT≤95%) had proliferating Ki67+ OX40+ T cells, CD69+ NK, exhausted CTLA4+ TIGIT+ T cells and pro-inflammatory CD16+ macrophages vs Non-Spontaneous Regressors (RVT>95%), enriched in highly activated Treg. In conclusion, neoadjuvant single dose A induced a CD8+/activated-myeloid profile that could relate to durable survival benefit. In T arm Responders showed activated/exhausted T cells and mature pro-inflammatory neutrophils, similar to Spontaneous Regressors in C arm; Non-Responders were enriched in senescent T cells and immunosuppressive myeloids. These results may indicate PD-1+/TIGIT+ exhausted T cells and pro-inflammatory myeloids as predictive biomarkers of A activity. Citation Format: Antonio Nuccio, Lydie Cassard, Nathalie Cozic, Malek Ben Salah, Vesna Lukic, Julien Adam, Wael Salem Zrafi, David Planchard, Jordi Remon, Pernelle Lavaud, Anas Gazzah, Vincent Thomas de Montpreville, Maria Rosa Ghigna, Patrick Dumont, Elie Fadel, Fabrice Barlesi, Caroline Caramella, Filippo Gustavo Dall’Olio, Olaf Mercier, Paul-Henry Cournède, Nathalie Chaput, Benjamin Besse. Single-dose neoadjuvant atezolizumab in resectable stage IA-IIIA non-N2 NSCLC: Tumor infiltrate analysis from the PRINCEPS trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7766.