First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial
机构：[1]Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.[2]Guangdong Lung Cancer Institute, Guangzhou, China.广东省人民医院[3]Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.[4]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing, China.[5]Sichuan Cancer Hospital, Chengdu, China.四川省肿瘤医院[6]Klinik Floridsdorf, Vienna Healthcare Group and Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Vienna, Austria.[7]Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.[8]Gustave Roussy, Paris-Saclay University, Villejuif, France.[9]Genesis Care, North Shore Health Hub and Northern Clinical School, University of Sydney, Sydney, Australia.[10]Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford, CA.[11]Kanagawa Cancer Center, Yokohama, Japan.[12]Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.广东省人民医院[13]City of Hope National Medical Center, Duarte, CA.[14]Department of Statistics and Quantitative Sciences, Takeda Development Center Americas, Inc, Lexington, MA.[15]Department of Clinical Science, Takeda Development Center Americas, Inc, Lexington, MA.[16]Department of Statistics, Cytel Inc, Cambridge, MA.[17]Department of Global Evidence and Outcomes Research, Takeda Development Center Americas, Inc, Lexington, MA.[18]Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Chinese University of China, Shatin, Hong Kong Special Administrative Region, China.
Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets EGFR exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of EGFR ex20ins+ advanced/metastatic NSCLC.Patients with treatment-naive EGFR ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; P = .803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with EGFR ex20ins+ advanced/metastatic NSCLC.
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大类|1 区医学
小类|1 区肿瘤学
第一作者：
第一作者机构：[1]Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
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推荐引用方式(GB/T 7714)：
Pasi A. J¨anne,Wang Bin-Chao,Cho Byoung Chul,et al.First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial[J].Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology.2025,JCO2401269.doi:10.1200/JCO-24-01269.
APA：
Pasi A. J¨anne,Wang Bin-Chao,Cho Byoung Chul,Zhao Jun,Li Juan...&Mok Tony S K.(2025).First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology,,
MLA：
Pasi A. J¨anne,et al."First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial".Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology .(2025):JCO2401269
医学