Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial
Background The phase II NEOMUN trial was conducted to investigate the therapeutic effect of preoperative programmed death receptor-1 inhibitor pembrolizumab for treating non-small cell lung cancer (NSCLC). Herein, we report the final efficacy, safety, and long-term survival results.Methods Patients...
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BMJ Publishing Group
2025-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/8/e011874.full |
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| author | Albrecht Stenzinger Dirk Jäger Michael Thomas Hauke Winter Helge Bischoff Uwe Haberkorn Felix Herth Pornpimol Charoentong Petros Christopoulos Rajkumar Savai Laura V Klotz Raffaella Griffo Martin E Eichhorn Florian Eichhorn Benedikt Niedermaier Philip Baum Michael Allgäuer Marc A Schneider Claus-Peter Heußel Maria Paula Roberti Inka Zoernig |
| author_facet | Albrecht Stenzinger Dirk Jäger Michael Thomas Hauke Winter Helge Bischoff Uwe Haberkorn Felix Herth Pornpimol Charoentong Petros Christopoulos Rajkumar Savai Laura V Klotz Raffaella Griffo Martin E Eichhorn Florian Eichhorn Benedikt Niedermaier Philip Baum Michael Allgäuer Marc A Schneider Claus-Peter Heußel Maria Paula Roberti Inka Zoernig |
| author_sort | Albrecht Stenzinger |
| collection | DOAJ |
| description | Background The phase II NEOMUN trial was conducted to investigate the therapeutic effect of preoperative programmed death receptor-1 inhibitor pembrolizumab for treating non-small cell lung cancer (NSCLC). Herein, we report the final efficacy, safety, and long-term survival results.Methods Patients with resectable stage II/IIIA NSCLC were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered before surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant treatment and evaluate antitumor activity. We analyzed the clinical parameters and pathologic, radiological, and metabolic tumor response data.Results 29 patients with NSCLC were enrolled. NSCLC histology revealed adenocarcinoma and squamous cell carcinoma in 24 and in 5 patients, respectively. 93.1% of patients were treated with two therapy cycles. 73 adverse events were reported, of which 18 were treatment-related. Complete tumor resection rate was 100%. Major (≤10% vital tumor cells) and complete pathologic response rates were 24.1% and 13.8%, respectively. Tumor response increased with higher programmed death-ligand 1 tumor proportion scores (TPS) and high pretherapeutic tumor mutational burden (≥10 mut./Mb). The metabolic response, quantified non-invasively using positron emission tomography/CT, predicted the pathologic tumor response. The disease-free survival was 75.9% at 24 and 36 months, and the overall survival was 82.7% at 24 and 36 months.Conclusions Neoadjuvant immunotherapy with pembrolizumab appears safe and feasible and is associated with a remarkable major pathologic response rate. Preoperative TPS, change in maximal standardized uptake value during the induction phase, and high mutational burden might be suitable clinical parameters for predicting pathologic response in surgical candidates.Trial registration number NCT0319746. |
| format | Article |
| id | doaj-art-b5cdbe0d8dce4179b3ff4c174503e303 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b5cdbe0d8dce4179b3ff4c174503e3032025-08-20T03:22:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2025-011874Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trialAlbrecht Stenzinger0Dirk Jäger1Michael Thomas2Hauke Winter3Helge Bischoff4Uwe Haberkorn5Felix Herth6Pornpimol Charoentong7Petros Christopoulos8Rajkumar Savai9Laura V Klotz10Raffaella Griffo11Martin E Eichhorn12Florian Eichhorn13Benedikt Niedermaier14Philip Baum15Michael Allgäuer16Marc A Schneider17Claus-Peter Heußel18Maria Paula Roberti19Inka Zoernig207 Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany4 Clinical Cooperation Unit Applied Tumor Immunity, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany10 Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany15 Department of Pulmonology and Critical Care Medicine, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany3 Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany13 Department of Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), Bad Nauheim, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany1 Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany2 Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany3 Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany3 Department of Medical Oncology and Internal Medicine VI, Heidelberg University Hospital, Heidelberg, GermanyBackground The phase II NEOMUN trial was conducted to investigate the therapeutic effect of preoperative programmed death receptor-1 inhibitor pembrolizumab for treating non-small cell lung cancer (NSCLC). Herein, we report the final efficacy, safety, and long-term survival results.Methods Patients with resectable stage II/IIIA NSCLC were included. Two cycles of pembrolizumab (200 mg intravenously once every 3 weeks) were administered before surgery. The primary objectives were to assess the feasibility and safety of neoadjuvant treatment and evaluate antitumor activity. We analyzed the clinical parameters and pathologic, radiological, and metabolic tumor response data.Results 29 patients with NSCLC were enrolled. NSCLC histology revealed adenocarcinoma and squamous cell carcinoma in 24 and in 5 patients, respectively. 93.1% of patients were treated with two therapy cycles. 73 adverse events were reported, of which 18 were treatment-related. Complete tumor resection rate was 100%. Major (≤10% vital tumor cells) and complete pathologic response rates were 24.1% and 13.8%, respectively. Tumor response increased with higher programmed death-ligand 1 tumor proportion scores (TPS) and high pretherapeutic tumor mutational burden (≥10 mut./Mb). The metabolic response, quantified non-invasively using positron emission tomography/CT, predicted the pathologic tumor response. The disease-free survival was 75.9% at 24 and 36 months, and the overall survival was 82.7% at 24 and 36 months.Conclusions Neoadjuvant immunotherapy with pembrolizumab appears safe and feasible and is associated with a remarkable major pathologic response rate. Preoperative TPS, change in maximal standardized uptake value during the induction phase, and high mutational burden might be suitable clinical parameters for predicting pathologic response in surgical candidates.Trial registration number NCT0319746.https://jitc.bmj.com/content/13/8/e011874.full |
| spellingShingle | Albrecht Stenzinger Dirk Jäger Michael Thomas Hauke Winter Helge Bischoff Uwe Haberkorn Felix Herth Pornpimol Charoentong Petros Christopoulos Rajkumar Savai Laura V Klotz Raffaella Griffo Martin E Eichhorn Florian Eichhorn Benedikt Niedermaier Philip Baum Michael Allgäuer Marc A Schneider Claus-Peter Heußel Maria Paula Roberti Inka Zoernig Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial Journal for ImmunoTherapy of Cancer |
| title | Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial |
| title_full | Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial |
| title_fullStr | Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial |
| title_full_unstemmed | Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial |
| title_short | Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial |
| title_sort | neoadjuvant anti programmed death 1 immunotherapy by pembrolizumab in resectable non small cell lung cancer results of the neomun trial |
| url | https://jitc.bmj.com/content/13/8/e011874.full |
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