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. 2025 Aug 5:S1556-0864(25)00983-9.
doi: 10.1016/j.jtho.2025.07.131. Online ahead of print.

Digital Versus Manual PD-L1 Scoring in Advanced NSCLC From the IMpower110 and IMpower150 Trials

Roy S Herbst  1 , Hen Prizant  2 , Daniel Ruderman  2 , Jake Conway  3 , John Shamshoian  3 , Hartmut Koeppen  2 , Wei Zou  2 , Filippo de Marinis  4 , Giuseppe Giaccone  5 , Jacek Jassem  6 , David R Spigel  7 , Mark A Socinski  8 , Martin Reck  9 , Luciana Molinero  2 , Marcus Ballinger  2 , David Shames  2 , Michael Griffin  3 , Limin Yu  3 , Nishant Agrawal  3 , Andrew Beck  3 , Ilan Wapinski  3 , Stephanie Hennek  3 , Jennifer Giltnane  2 , Minu K Srivastava  2
Affiliations

Digital Versus Manual PD-L1 Scoring in Advanced NSCLC From the IMpower110 and IMpower150 Trials

Roy S Herbst et al. J Thorac Oncol. .

Abstract

Introduction: Treatment selection in patients with advanced NSCLC is based on programmed death-ligand 1 (PD-L1) expression, which is usually scored manually and is subject to intra- and inter-pathologist variability. A PD-L1 clone-agnostic artificial intelligence (AI) model for AI-based measurement of PD-L1 (AIM-PD-L1) was developed and assessed in advanced NSCLC using clinical samples from two phase 3 trials.

Methods: IMpower110 evaluated atezolizumab versus chemotherapy in PD-L1-positive metastatic, stage IV, squamous or nonsquamous NSCLC. IMpower150 evaluated atezolizumab, carboplatin, and paclitaxel, with or without bevacizumab, versus carboplatin, paclitaxel, and bevacizumab in patients with metastatic nonsquamous NSCLC. AIM-PD-L1 was developed and deployed on SP263-stained whole slide images (IMpower110, n = 509; IMpower150, n = 766) for digital scoring of tumor cell (TC) PD-L1 expression and identification of human-interpretable features (HIFs) associated with survival outcomes.

Results: Overall percentage agreements between scoring methods for TC more than or equal to 50% and more than or equal to 1% cutoffs were high. Survival analyses were similar for PD-L1 subgroups between scoring methods at both TC cutoffs. A nonsignificant improvement in survival outcomes was observed in patients treated with atezolizumab-containing regimens and classified as positive by digital scoring but missed by manual scoring. Two HIFs in the cancer epithelium-density of all PD-L1-positive TC and immune cells-were nominally associated with overall survival. Many HIFs were identified to be predictive of significantly improved progression-free survival with atezolizumab-containing regimens versus control.

Conclusions: AIM-PD-L1 digital SP263 PD-L1 scoring is concordant with manual scoring, revealing similar predictivity for benefit, and could potentially be used as a predictive marker for patient stratification and selection for anti-PD-(L)1 therapy.

Keywords: AIM-PD-L1; Advanced or metastatic NSCLC; Digital pathology; Non–small cell lung cancer.

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Conflict of interest statement

Disclosure All authors report receiving research support in the form of third-party writing assistance for this manuscript from F. Hoffmann-La Roche Ltd. Dr. Herbst reports receiving grants from AstraZeneca, Eli Lilly, Genentech/Roche, and Merck Sharp & Dohme; consultant fees from Amgen, Arrivent BioPharma, AstraZeneca, Bristol Myers Squibb, Candel Therapeutics, Catalym, Checkpoint Therapeutics, Eli Lilly, Genentech, Gilead Sciences, I-Mab Biopharma, Immunocore, Janssen, Mediflix, Merck Serono, Merck Sharp & Dohme, NextCure, Novartis, Pfizer, Regeneron, Roche, and Sanofi; outside the current work; advisory board fees from AstraZeneca, Candel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, I-Mab Biopharma, Immune-Onc Therapeutics Immunocore, and Novartis; travel fees from AstraZeneca, Genentech/Roche, and Merck Sharpe & Dohme; is a stock owner of Bolt Biotherapeutics, Checkpoint Therapeutics, and Immunocore; is a non-executive board member for Immunocore and Junshi Pharmaceuticals; and declares a fiduciary role with American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, and Southwest Oncology Group Friends of Cancer Research, outside the current work. Dr. Prizant is an employee of Genentech; reports receiving travel fees from Genentech/Roche; and is a stock owner of Roche, outside the current work. Dr. Ruderman is an employee of Genentech; reports receiving travel fees from Genentech; is a stock owner of Roche; and has patents from Genentech, outside the current work. Dr. Conway is an employee of PathAI and reports receiving travel fees from PathAI, outside the current work. Drs. Shamshioan and Agrawal are employees of PathAI and are stock owners of PathAI, outside the current work. Drs. Koeppen, Zou, Molinero, Ballinger, and Srivastava are employees of Genentech and are stock owners of Roche, outside the current work. Dr. de Marinis received advisory fees from AstraZeneca, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, and Regeneron, outside the current work. Dr. Giaccone has no other disclosures to declare. Dr. Jassem received consulting fees from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Roche; honorarium from AstraZeneca, Merck Sharp & Dohme, Novartis, and Pfizer; travel fees from AstraZeneca, Novartis, Pfizer, and Takeda; advisory fees from Graegis, outside the current work. Dr. Spigel reports receiving institutional research funding from AbbVie, Agios, Amgen, AnHeart Therapeutics, Apollomics, Arcus Biosciences, Arrys Therapeutics, Ascendis Pharma, Asher Bio, Astellas, AstraZeneca, Bayer, BeOne Medicines, BioNTech, Blueprint Medicine, Boehringer-Ingelheim, Bristol Myers Squibb, Chugai Pharmaceuticals, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, Ellipses Pharma, Endeavor BioMedicines, Eli Lilly, Erasca, Faeth Therapeutics, Gilead Sciences, GlaxoSmithKline, GRAIL, Hutchinson Medipharma, Incyte, Inspirna, Ipsen, Janssen, Janux Therapeutics, Jazz Pharmaceuticals, Kronos Bio, Loxo Oncology, Lyell Immunopharma, MacroGenics, Merck Serono, Merck Sharpe & Dohme, Moderna, Molecular Templates, Monte Rosa Therapeutics, Nektar Therapeutics, Novartis, Novocure, Phanes Therapeutics, PTC Therapeutics, Puretech Health, Razor Genomics, Repare Therapeutics, Roche/Genentech, Seagen, Shenzhen Chipscreen Biosciences, Strata Oncology, Stemline Therapeutics, Synthekine, Taiho, Takeda, Tango Therapeutics, Tarveda Therapeutics, Tizona Therapeutics, Verastem Oncology, and Zai Lab; and advisory role fees from AbbVie, Amgen, AstraZeneca, Circle Pharma, Daiichi Sankyo, GlaxoSmithKline, Jazz Pharmaceuticals, Lyell Immunopharma, ModeX Therapeutics, Novartis, Novocure, Pyxis Oncology, and Roche/Genentech, outside the current work. Dr. Socinski reports receiving grants from AstraZeneca, BeOne Medicines, Enliven Therapeutics, OncoC4, and Spectrum Pharma; consulting fees from BeOne Medicines, Eli Lilly, OncoC4, and Summit Pharma; honorarium from AstraZeneca, Jazz Pharmaceuticals, Eli Lilly, Guardant Health, Genentech, and Merck Sharpe & Dohme; and advisory fees from Bristol-Myers Squibb and Summit Pharma; and declares a fiduciary role with Elsevier, outside of this current work. Dr. Reck has received consulting fees from Amgen, AstraZeneca, BeOne Medicines, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Mirati Therapeutics, Novartis, Pfizer, Roche, Regeneron, and Sanofi; honorarium from Amgen, AstraZeneca, BeOne Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Mirati Therapeutics, Merck Sharpe & Dohme, Novartis, Pfizer, Roche, Regeneron, and Sanofi; travel fees from Amgen, AstraZeneca, BeOne Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Mirati Therapeutics, Novartis, Pfizer, Roche, Regeneron, and Sanofi; and advisory fees from Daiichi Sankyo and Sanofi, outside the current work. Dr. Shames is an employee of BeOne Medicines and is a stock owner of BeOne Medicines and Roche. Dr. Griffin is an employee of PathAI, outside the current work. Drs. Yu and Beck are employees of Genentech, outside the current work. Dr. Wapinski is an employee of PathAI and Sanofi; reports receiving honorarium from FOCIS Systems Immunology workshop; and is a stock owner of PathAI and Sanofi, outside the current work. Dr. Henneck is an employee of Genentech; receives royalties from Sanofi; and is a stock owner of PathAI and Vizgen, outside the current work. Dr. Giltnane is an employee of GlaxoSmithKline and is a stock owner of Roche, outside the current work.

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