First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial
Abstract Background The ASTRUM‐005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive‐stage small‐cell lung cancer (ES‐SCLC). Here, we report updated...
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2025-08-01
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| author | Ying Cheng Shuang Zhang Liang Han Lin Wu Jun Chen Peiyan Zhao Hongmei Sun Guilan Wen Yinghua Ji Anastasia Zimina Jianhua Shi Zhijie Pan Jinsheng Shi Xicheng Wang Yuansong Bai Tamar Melkadze Yueyin Pan Xuhong Min Maksym Viguro Xingya Li Yanqiu Zhao Junquan Yang Tamta Makharadze Ekaterine Arkania Haoyu Yu Jing Li Fang Yang Xinyi Yang Chen Ling Qingyu Wang Yongqiang Shan Jun Zhu the ASTRUM‐005 Study Group |
| author_facet | Ying Cheng Shuang Zhang Liang Han Lin Wu Jun Chen Peiyan Zhao Hongmei Sun Guilan Wen Yinghua Ji Anastasia Zimina Jianhua Shi Zhijie Pan Jinsheng Shi Xicheng Wang Yuansong Bai Tamar Melkadze Yueyin Pan Xuhong Min Maksym Viguro Xingya Li Yanqiu Zhao Junquan Yang Tamta Makharadze Ekaterine Arkania Haoyu Yu Jing Li Fang Yang Xinyi Yang Chen Ling Qingyu Wang Yongqiang Shan Jun Zhu the ASTRUM‐005 Study Group |
| author_sort | Ying Cheng |
| collection | DOAJ |
| description | Abstract Background The ASTRUM‐005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive‐stage small‐cell lung cancer (ES‐SCLC). Here, we report updated efficacy and safety results after an extended median follow‐up of 19.8 months, along with the first report on findings from exploratory biomarker analyses. Methods A total of 585 patients were randomized in a 2:1 ratio to receive 4.5 mg/kg serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks, together with carboplatin and etoposide. The primary endpoint was OS. In addition, genomic profiling was performed to identify mutated genes, and quantitative serum proteome profiling was conducted to identify differentially expressed proteins (DEPs) between responders and non‐responders of serplulimab plus chemotherapy. Regression analysis was subsequently used to construct a protein signature based on the DEPs. The associations between efficacy outcomes (objective response rate [ORR], OS, and progression‐free survival [PFS]) and gene mutation status or DEP expression were also examined with regression analysis. Furthermore, the prognostic value of hematological parameters was evaluated. Results In the intent‐to‐treat population, the median OS was 15.8 months in the serplulimab group versus 11.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval, 0.50‐0.76; P < 0.001). We identified 181 DEPs between responders and non‐responders in the serplulimab group, from which a 15‐protein signature was constructed. In the serplulimab group, patients with a higher 15‐protein signature score were associated with significantly longer OS and PFS. Also, patients harboring tumor‐suppressor retinoblastoma‐1 (RB1) mutations or mutations in Notch pathway members showed improved ORR, OS, or PFS compared with their wild‐type counterparts. Baseline neutrophil‐to‐lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level were independent prognosticators of patients with ES‐SCLC. Conclusions First‐line serplulimab provided a sustained clinical benefit over placebo in patients with ES‐SCLC. A 15‐protein signature and mutations in RB1 or Notch pathway genes may serve as predictive biomarkers for benefits from serplulimab plus chemotherapy, while baseline NLR and LDH were independent prognosticators for ES‐SCLC. |
| format | Article |
| id | doaj-art-2fa6a04a4d364f3db669c899997fe334 |
| institution | Kabale University |
| issn | 2523-3548 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| series | Cancer Communications |
| spelling | doaj-art-2fa6a04a4d364f3db669c899997fe3342025-08-20T08:40:33ZengWileyCancer Communications2523-35482025-08-01458990100910.1002/cac2.70032First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trialYing Cheng0Shuang Zhang1Liang Han2Lin Wu3Jun Chen4Peiyan Zhao5Hongmei Sun6Guilan Wen7Yinghua Ji8Anastasia Zimina9Jianhua Shi10Zhijie Pan11Jinsheng Shi12Xicheng Wang13Yuansong Bai14Tamar Melkadze15Yueyin Pan16Xuhong Min17Maksym Viguro18Xingya Li19Yanqiu Zhao20Junquan Yang21Tamta Makharadze22Ekaterine Arkania23Haoyu Yu24Jing Li25Fang Yang26Xinyi Yang27Chen Ling28Qingyu Wang29Yongqiang Shan30Jun Zhu31the ASTRUM‐005 Study GroupDepartment of Oncology Jilin Cancer Hospital Changchun Jilin P. R. ChinaDepartment of Oncology Jilin Cancer Hospital Changchun Jilin P. R. ChinaDepartment of Oncology Xuzhou Central Hospital Xuzhou Jiangsu P. R. ChinaDepartment of Thoracic Medical Oncology Hunan Cancer Hospital, the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University Changsha Hunan P. R. ChinaDepartment of Lung Cancer Surgery Tianjin Medical University General Hospital Tianjin P. R. ChinaDepartment of Oncology Jilin Cancer Hospital Changchun Jilin P. R. ChinaDepartment of Oncology Jiamusi Cancer Hospital Jiamusi Heilongjiang P. R. ChinaDepartment of Respiratory Medicine The First Affiliated Hospital of Nanchang University Nanchang Jiangxi P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Xinxiang Medical University Xinxiang Henan P. R. ChinaDepartment of Oncology Budgetary Healthcare Institution of Omsk Region “Clinical Oncology Dispensary” Omsk RussiaDepartment of Oncology Linyi Cancer Hospital Linyi Shandong P. R. ChinaDepartment of Respiratory Medicine The First Affiliated Hospital of Zhejiang University School of Medicine Hangzhou Zhejiang P. R. ChinaDepartment of Oncology Cangzhou People's Hospital Cangzhou Hebei P. R. ChinaDepartment of Oncology The First Affiliated Hospital of Guangdong Pharmaceutical University Guangzhou Guangdong P. R. ChinaDepartment of Oncology and Hematology China‐Japan Union Hospital of Jilin University Changchun Jilin P. R. ChinaAcademician Fridon Todua Medical Center–Research Institute of Clinical Medicine Tbilisi GeorgiaDepartment of Oncology Anhui Provincial Hospital Hefei Anhui P. R. ChinaDepartment of Interventional Radiology Anhui Chest Hospital Hefei Anhui P. R. ChinaClinical Research Department Medical Center “Mriya Med‐Service” Kryvyi Rih UkraineDepartment of Oncology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan P. R. ChinaRespiratory Department of Internal Medicine The Affiliated Cancer Hospital of Zhengzhou University Zhengzhou Henan P. R. ChinaDepartment of Oncology Tangshan People's Hospital Tangshan Hebei P. R. ChinaDepartment of Oncology‐Endocrinology High Technology Hospital MedCenter Batumi GeorgiaDepartment of Oncology Israeli‐Georgian Medical Research Clinic “Helsicore” Tbilisi GeorgiaDepartment of Global Product Development Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaDepartment of Global Product Development Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaShanghai Innovation Center Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaShanghai Innovation Center Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaShanghai Innovation Center Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaDepartment of Global Product Development Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaShanghai Innovation Center Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaChairperson of the Board Office Shanghai Henlius Biotech, Inc. Shanghai P. R. ChinaAbstract Background The ASTRUM‐005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive‐stage small‐cell lung cancer (ES‐SCLC). Here, we report updated efficacy and safety results after an extended median follow‐up of 19.8 months, along with the first report on findings from exploratory biomarker analyses. Methods A total of 585 patients were randomized in a 2:1 ratio to receive 4.5 mg/kg serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks, together with carboplatin and etoposide. The primary endpoint was OS. In addition, genomic profiling was performed to identify mutated genes, and quantitative serum proteome profiling was conducted to identify differentially expressed proteins (DEPs) between responders and non‐responders of serplulimab plus chemotherapy. Regression analysis was subsequently used to construct a protein signature based on the DEPs. The associations between efficacy outcomes (objective response rate [ORR], OS, and progression‐free survival [PFS]) and gene mutation status or DEP expression were also examined with regression analysis. Furthermore, the prognostic value of hematological parameters was evaluated. Results In the intent‐to‐treat population, the median OS was 15.8 months in the serplulimab group versus 11.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval, 0.50‐0.76; P < 0.001). We identified 181 DEPs between responders and non‐responders in the serplulimab group, from which a 15‐protein signature was constructed. In the serplulimab group, patients with a higher 15‐protein signature score were associated with significantly longer OS and PFS. Also, patients harboring tumor‐suppressor retinoblastoma‐1 (RB1) mutations or mutations in Notch pathway members showed improved ORR, OS, or PFS compared with their wild‐type counterparts. Baseline neutrophil‐to‐lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level were independent prognosticators of patients with ES‐SCLC. Conclusions First‐line serplulimab provided a sustained clinical benefit over placebo in patients with ES‐SCLC. A 15‐protein signature and mutations in RB1 or Notch pathway genes may serve as predictive biomarkers for benefits from serplulimab plus chemotherapy, while baseline NLR and LDH were independent prognosticators for ES‐SCLC.https://doi.org/10.1002/cac2.70032SerplulimabES‐SCLCASTRUM‐005phase 3 |
| spellingShingle | Ying Cheng Shuang Zhang Liang Han Lin Wu Jun Chen Peiyan Zhao Hongmei Sun Guilan Wen Yinghua Ji Anastasia Zimina Jianhua Shi Zhijie Pan Jinsheng Shi Xicheng Wang Yuansong Bai Tamar Melkadze Yueyin Pan Xuhong Min Maksym Viguro Xingya Li Yanqiu Zhao Junquan Yang Tamta Makharadze Ekaterine Arkania Haoyu Yu Jing Li Fang Yang Xinyi Yang Chen Ling Qingyu Wang Yongqiang Shan Jun Zhu the ASTRUM‐005 Study Group First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial Cancer Communications Serplulimab ES‐SCLC ASTRUM‐005 phase 3 |
| title | First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial |
| title_full | First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial |
| title_fullStr | First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial |
| title_full_unstemmed | First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial |
| title_short | First‐line serplulimab plus chemotherapy in extensive‐stage small‐cell lung cancer: Updated results and biomarker analysis from the ASTRUM‐005 randomized clinical trial |
| title_sort | first line serplulimab plus chemotherapy in extensive stage small cell lung cancer updated results and biomarker analysis from the astrum 005 randomized clinical trial |
| topic | Serplulimab ES‐SCLC ASTRUM‐005 phase 3 |
| url | https://doi.org/10.1002/cac2.70032 |
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