Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2018
Phase Ib/II Study of Capmatinib (INC280) Plus Gefitinib After Failure of Epidermal Growth Factor Receptor (EGFR) Inhibitor Therapy in Patients With EGFR-Mutated, MET Factor-Dysregulated Non-Small-Cell Lung Cancer.
Erratum issuedOpen access · greenAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 206 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
206citing papers in PubMed, 3 pooled it
26.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
206 citing papers in PubMed, 3 syntheses or guidelines pooled it, 329 citations in OpenAlex.
- Pooled it
- Non-small cell lung cancer withFrontiers in oncology · 2023Pooled it
- MET-Targeted Therapies and Clinical Outcomes: A Systematic Literature Review.Molecular diagnosis & therapy · 2022Pooled it
- A prospective, multicenter, comprehensive genomic profile signature study in patients with EGFR-mutant advanced non-small cell lung cancer at the first-line treatment failure of osimertinib.Signal transduction and targeted therapy · 2025Trial
- Randomized Trial of Tepotinib Plus Gefitinib versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Capmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study.Cancer science · 2021Trial
- A Phase Ib/II, open-label, multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma.Journal of neuro-oncology · 2020Trial
- C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.Signal transduction and targeted therapy · 2026Review
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- MET Dependence Oversteps EGFR Dependence via Balancing Dimerization of the Receptor Tyrosine Kinases in Osimertinib-Resistant MET-Amplified, EGFR-Mutated Non-Small Cell Lung Cancer.Thoracic cancer · 2026Article
- [Chinese Expert Consensus on Diagnosis and Treatment of Non-small Cell Lung Cancer with MET Abnormality (2026 Version)].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Epidermal growth factor receptor tyrosine kinase inhibitor for the treatment of non-small cell lung cancer in the past 30 years (1997-2026).Chinese medical journal · 2026Review
- Atrial fibrillation associated with tyrosine kinase inhibitors: A case-control study of real-world pharmacovigilance data.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- First Line and Treatment Sequencing in EGFR-Mutated Metastatic NSCLC: What is Right for Which Patient?Drugs · 2026Review
- Review
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Exploratory Identification of Gene Copy Number Cut-Off for NGS-BasedLung Cancer (Auckland, N.Z.) · 2026Article
- MET Exon 14 Skipping Mutation in NSCLC: From Genomic Discovery to Biomarker-Guided Therapeutic Innovation.Current drug targets · 2026Review
- Fatal Disease Progression Driven by Acquired MET Amplification After EGFR-TKI Therapy in EGFR- and RBM10-Mutant Lung Adenocarcinoma.Cancer management and research · 2026Article
- Case Report: Remarkable response to savolitinib plus chemotherapy and bevacizumab in second-line treatment of MET amplified colon cancer with liver metastasis.Frontiers in oncology · 2026Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on byExploiting2018
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- Erratum issuedErrata.2019
Authors and funding
17 authors at 1 institution in 1 country.
Yi-Long WuYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Li ZhangYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Dong-Wan KimYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Xiaoqing LiuYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Dae Ho LeeYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
James Chih-Hsin YangYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Myung-Ju AhnYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Johan F VansteenkisteYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Wu-Chou SuYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Enriqueta FelipYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Vincent ChiaYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Sabine GlaserYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Philippe PultarYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Sylvia ZhaoYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Bin PengYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Mikhail AkimovYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Daniel S W TanYi-Long Wu, Guangdong General Hospital and Guangdong Academy of Medical Sciences; Li Zhang, Sun Yat-sen University Cancer Center, Guangdong; Xiaoqing Liu, Affiliated Hospital of the Chinese Academy of Military Medical Sciences, Beijing; Sylvia Zhao and Bin Peng, Novartis Institutes for Biomedical Research, Shanghai, People's Republic of China; Dong-Wan Kim, Seoul National University Hospital; Dae Ho Lee, University of Ulsan College of Medicine; Myung-Ju Ahn, Samsung Medical Center, Seoul, Republic of Korea; James Chih-Hsin Yang, National Taiwan University Hospital, Taipei; Wu-Chou Su, National Cheng Kung University Hospital, Tainan, Taiwan; Johan F. Vansteenkiste, University Hospital KU Leuven, Leuven, Belgium; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Vincent Chia and Philippe Pultar, Novartis Pharmaceuticals, East Hanover, NJ; Sabine Glaser and Mikhail Akimov, Novartis Pharma AG, Basel, Switzerland; and Daniel S.W. Tan, National Cancer Centre Singapore, Singapore.
Chinese Academy of Medical Sciences & Peking Union Medical College · CN
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMET dysregulation occurs in up to 26% of non-small-cell lung cancers (NSCLCs) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment. Capmatinib (INC280) is a potent and selective MET inhibitor with preclinical activity in combination with gefitinib in EGFR-mutant, MET-amplified/overexpressing models of acquired EGFR-TKI resistance. This phase Ib/II study investigated the safety and efficacy of capmatinib plus gefitinib in patients with EGFR-mutated, MET-dysregulated (amplified/overexpressing) NSCLC who experienced disease progression while receiving EGFR-TKI treatment.
methodsPatients in phase Ib received capmatinib 100- to 800-mg capsules once per day or 200- to 600-mg capsules or tablets twice per day, plus gefitinib 250 mg once per day. Patients in phase II received the recommended phase II dose. The primary end point was the overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
resultsSixty-one patients were treated in phase Ib, and 100 were treated in phase II. The recommended phase II dose was capmatinib 400 mg twice per day plus gefitinib 250 mg once per day. Preliminary clinical activity was observed, with an ORR across phase Ib/II of 27%. Increased activity was seen in patients with high MET-amplified tumors, with a phase II ORR of 47% in patients with a MET gene copy number ≥ 6. Across phases Ib and II, the most common drug-related adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%); the most common drug-related grade 3/4 adverse events were increased amylase and lipase levels (both 6%). No significant drug-drug interactions between capmatinib and gefitinib were evident.
conclusionThis study, focused on a predominant EGFR-TKI resistance mechanism in patients with EGFR-mutated NSCLC, shows that the combination of capmatinib with gefitinib is a promising treatment for patients with EGFR-mutated, MET-dysregulated NSCLC, particularly MET-amplified disease.
Indexed as
AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, Non-Small-Cell LungErbB ReceptorsFemaleGefitinibHumansImidazolesLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMutationProto-Oncogene Proteins c-metBenzamidescapmatinibEGFR protein, humanErbB ReceptorsGefitinibImidazolesMET protein, humanProto-Oncogene Proteins c-metTriazines
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