Abstract
Patients with resectable non-small cell lung cancer (NSCLC) remain at high risk of relapse despite perioperative treatment1-3. NeoCOAST-2 (NCT05061550), a phase 2, randomised platform trial, tested novel perioperative treatments in patients with stage IIA–IIIB NSCLC. At primary analysis, combining standard chemotherapy plus durvalumab (anti-PD-L1 antibody) with oleclumab (Arm 1, n = 76), monalizumab (Arm 2, n = 72) or datopotamab deruxtecan (Dato-DXd; Arm 4, n = 54) resulted in pathological complete response (pCR) rates of 20.3%, 25.7%, and 35.2%, respectively4. Here, we present the first report of prespecified secondary endpoints of event-free survival (EFS) and circulating tumour DNA (ctDNA) clearance, and exploratory analyses of associations between ctDNA dynamics and clinical outcomes. The 24-month EFS rates were 70.5%, 75.7% and 77.9% in Arms 1, 2 and 4, respectively. Using a tumour-agnostic assay, ctDNA clearance at neoadjuvant Cycle 3 Day 1 was highest in Arm 4 (50.9%, 54.5%, and 72.5% in each arm, respectively). ctDNA clearance correlated with prolonged EFS versus non-clearance (pooled hazard ratio (HR) 0.22; 95% CI = 0.11–0.45, P = 0.0000443). Patients with both ctDNA clearance and pCR had favourable EFS outcomes versus those with neither (EFS HR 0.10, 95% CI = 0.02–0.42, P = 0.002). These findings suggest combined assessment of ctDNA clearance and pCR may improve risk stratification, and that the numerically highest pCR4 and EFS rates with the Dato-DXd combination warrant further evaluation.
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Author information
Authors and Affiliations
Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, MA, USA
Lara McGrath
Translational Medicine, Early Data Science, Oncology R&D, AstraZeneca, Cambridge, UK
Gozde Kar
Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
Laura Bonanno
Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy
Laura Bonanno
Univ Rouen Normandie, LITIS Lab QuantIF team EA4108, CHU Rouen, Department of Pneumology and Inserm CIC-CRB 1404, Rouen, France
Florian Guisier
Medical Oncology Department, Hospital Clínico Universitario de Valencia, Valencia, Spain
Amelia Insa
Division of Thoracic Surgery, University of Montréal, Montréal, Quebec, Canada
Moishe Liberman
CETOC - CHUM Endoscopic Tracheobronchial and Oesophageal Center, Centre Hospitalier de l’Université de Montréal, Montreal, Quebec, Canada
Moishe Liberman
Pneumology Department, Hôpital d’Instruction des Armées Sainte-Anne, Toulon, France
Olivier Bylicki
Department of Radiation Oncology, University of Florence, Florence, Italy
Lorenzo Livi
Department of Thoracic Oncology, Dupuytren University Hospital, Limoges, France
Thomas Egenod
Department of Medical Oncology, CH de Cornouaille, Quimper, France
Romain Corre
Department of Internal Medicine, Seoul National University College of Medicine and Seoul National Hospital, Seoul, South Korea
Dong-Wan Kim
Hospital de A Coruña, Sergas, A Coruña, Spain
Maria Rosario Garcia Campelo
Puerta de Hierro University Hospital, Majadahonda, Spain
Mariano Provencio Pulla
Department of Medical Oncology, The Catholic University of Korea, St. Vincent’s Hospital, Seoul, South Korea
Byoung Yong Shim
Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
Giulio Metro
Department of Medical Oncology, Hôpital Foch, Suresnes, France
Jaafar Bennouna
Early Clinical Development, Oncology R&D, AstraZeneca, Cambridge, MA, USA
Agata A. Bielska & Italia Grenga
Early Clinical Development, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA
Alula R. Yohannes & Joanna Shaju
Early Oncology Biometrics, Oncology R&D, AstraZeneca, Cambridge, MA, USA
Yun He
Early Clinical Programs, Oncology R&D, AstraZeneca, Cambridge, UK
Adam Dowson
Department of Thoracic Surgery, McGill University, Montreal, Quebec, Canada
Jonathan Spicer
Trinity St. James’s Cancer Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland
Patrick M. Forde
Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Tina Cascone
Authors
- Lara McGrath
- Gozde Kar
- Laura Bonanno
- Florian Guisier
- Amelia Insa
- Moishe Liberman
- Olivier Bylicki
- Lorenzo Livi
- Thomas Egenod
- Romain Corre
- Dong-Wan Kim
- Maria Rosario Garcia Campelo
- Mariano Provencio Pulla
- Byoung Yong Shim
- Giulio Metro
- Jaafar Bennouna
- Agata A. Bielska
- Alula R. Yohannes
- Joanna Shaju
- Yun He
- Adam Dowson
- Italia Grenga
- Jonathan Spicer
- Patrick M. Forde
- Tina Cascone
Corresponding author
Correspondence to Tina Cascone.
About this article
Cite this article
McGrath, L., Kar, G., Bonanno, L. et al. ctDNA clearance and outcomes for resectable lung cancer from NeoCOAST-2. Nature (2026). https://doi.org/10.1038/s41586-026-11328-3
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DOI: https://doi.org/10.1038/s41586-026-11328-3