N Engl J Med. 2025;393(18):1819-1832.
Sevabertinib in Advanced HER2-Mutant Non-Small-Cell Lung Cancer.
제1저자 Xiuning Le, 김태민 · 교신저자 Xiuning Le
소속 (32)
- M.D. Anderson Cancer Center, Houston.
- Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
- Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong.
- Phase 1 Clinical Trial Center, Chinese University of Hong Kong, Hong Kong.
- Oncologia Medica Toracica Dipartimento, Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan.
- Department of Hematology-Oncology, National University Cancer Institute, Singapore.
- Cancer Science Institute of Singapore, National University of Singapore, Singapore.
- Department of Medical Oncology, Beijing Hospital, Beijing.
- National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing.
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
- Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
- Department of Thoracic Medical Oncology, Hunan Cancer Hospital, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
- National Cancer Center Hospital, Tokyo.
- Phase 1 Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome.
- Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
- Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Seoul, South Korea.
- Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea.
- Departments of Clinical Pharmacology and Thoracic Oncology, Netherlands Cancer Institute, Amsterdam.
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Department I of Thoracic Oncology, Peking University Cancer Hospital and Institute, Beijing.
- Department of Oncology, Azienda Ospedaliero-Universitaria San Luigi Gonzaga, Turin, Italy.
- Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
- Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston.
- National Cancer Center Hospital East, Kashiwa, Japan.
- Bayer, Berlin.
- Bayer, Reading, United Kingdom.
- Bayer Consumer Care, Basel, Switzerland.
- Bayer HealthCare Pharmaceuticals, Whippany, NJ.
- Bayer, Milan.
- Institut Curie, Paris.
- National Cancer Center Singapore, Singapore.
- Duke-National University of Singapore Medical School, Singapore.
Abstract
BACKGROUND HER2 gene mutations occur in 2 to 4% of patients with non-small-cell lung cancer (NSCLC). Sevabertinib is an oral, reversible tyrosine kinase inhibitor that has shown anti-HER2 activity in preclinical models.
METHODS We conducted an open-label, multicenter, multicohort, phase 1-2 study to evaluate sevabertinib at a twice-daily dose of 20 mg in patients with locally advanced or metastatic HER2-mutant NSCLC. Three cohorts were defined according to previous therapy: cohort D comprised previously treated patients who had not received HER2-targeted therapy; cohort E, patients who had previously received HER2-directed antibody-drug conjugates; and cohort F, patients who had not previously received treatment. The primary end point was an objective response, as assessed by blinded independent central review. Secondary end points were duration of response and progression-free survival.
RESULTS A total of 209 patients received sevabertinib (as of June 27, 2025, the data-cutoff date); the median duration of follow-up was 13.8 months in cohort D, 11.7 months in cohort E, and 9.9 months in cohort F. Among 81 patients in cohort D, an objective response was observed in 64% (95% confidence interval [CI], 53 to 75); the median duration of response was 9.2 months (95% CI, 6.3 to 13.5), and the median progression-free survival was 8.3 months (95% CI, 6.9 to 12.3). Among 55 patients in cohort E, an objective response was observed in 38% (95% CI, 25 to 52); the median duration of response was 8.5 months, and the median progression-free survival was 5.5 months. Among 73 patients in cohort F, an objective response was observed in 71% (95% CI, 59 to 81), and the median duration of response was 11.0 months; data on progression-free survival were immature. Grade 3 or higher drug-related adverse events occurred in 31% of the patients. The most common adverse event was diarrhea (in 84 to 91%), with diarrhea of grade 3 or higher occurring in 5 to 23%. Treatment was discontinued by 3% of the patients owing to drug-related adverse events.
CONCLUSIONS Sevabertinib showed antitumor activity in patients with locally advanced or metastatic HER2-mutant NSCLC. Diarrhea was the most common adverse event. (Funded by Bayer; SOHO-01 ClinicalTrials.gov number, NCT05099172.).
Copyright © 2025 Massachusetts Medical Society.
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그 밖의 정보
- 출판 형태
- Journal Article, Multicenter Study, Clinical Trial, Phase I, Clinical Trial, Phase II
- 저널
- The New England journal of medicine · eISSN 1533-4406
- 전자 출판
- 2025-10-17
- MeSH
- Adult · Aged · Aged, 80 and over · Female · Humans · Male · Middle Aged · Antineoplastic Agents* / administration & dosage / adverse effects · Carcinoma, Non-Small-Cell Lung* / drug therapy / genetics / mortality / secondary · Lung Neoplasms* / drug therapy / genetics / mortality / pathology · Mutation · Progression-Free Survival · Erb-b2 Receptor Tyrosine Kinases* / genetics / antagonists & inhibitors · Tyrosine Kinase Inhibitors* / administration & dosage / adverse effects · Time Factors · Diarrhea / chemically induced / epidemiology · Neoplasm Staging · Administration, Oral
- Substances
- Antineoplastic Agents · Erb-b2 Receptor Tyrosine Kinases · Tyrosine Kinase Inhibitors · ERBB2 protein, human
- 데이터
- ClinicalTrials.gov: NCT05099172